Birthmarks, Moles, and Skin Cancer

Birthmarks and moles are distinctive congenital or acquired skin lesions. The majority of the time they are benign, isolated findings. Occasionally, they may be part of a syndrome or have the potential for malignant transformation. Pediatric dermatologists are trained to recognize distinguishing features of these characteristic skin lesions. Although rare in children, skin cancer is also discussed.

The following topics are reviewed in this section:

• Café au Lait Macules

• Congenital Dermal Melanocytosis

• Congenital Melanocytic Nevus

• Acquired Nevi

• Skin Cancer

Café au Lait Macules

Café au lait macules (CALMs) are flat, lightly hyperpigmented, well-circumscribed macules and patches that can be light brown in light-skinned patients or medium-to-dark brown in darker-skinned patients. They are usually round to oval in shape but may have geometric configurations. The size is highly variable.

Café au lait macules are well-circumscribed, usually round-to-oval shaped, and uniform light-brown color. (Photograph courtesy of Carol Cheng, MD.)

CALMs are common in the general population, and in most children they represent a benign finding. The prevalence of CALMs is higher in people with darker skin types. The prevalence of CALMs in newborns varies with race from 0.3% in whites to 18% in Blacks. In school-aged children, the prevalence increases to 13% in whites and 27% in Blacks. Multiple CALMs can serve as a marker of genodermatoses. For example, multiple CALMs associated with axillary or inguinal freckling raise suspicion for neurofibromatosis type 1. CALMs can be associated with different neurocutaneous conditions and other syndromes, as described in this review.

Associated Syndromes

• Neurofibromatosis type 1 (NF1)

  • One of the diagnostic criteria for NF1 is multiple CALMs.

  • The lesions are generally present by age 4 years and persist into adulthood.

  • The presence of ≥6 CALMs ≥5 mm in prepubescent patients and ≥15 mm in postpubescent patients is suggestive of NF1 and should prompt further workup with genetic testing.

• Neurofibromatosis type 2

• Legius syndrome (NF1-like syndrome)

• McCune-Albright syndrome

  • Large and segmental darker CALMs with jagged borders are often present overlying the trunk.

• Watson syndrome

• Noonan syndrome with multiple lentigines (formerly known as LEOPARD syndrome)

  • CALMs are often dark brown (cafe noir macules)

• Ring chromosome syndromes

  • CALMs are rare but have been reported with ring chromosome syndromes involving chromosomes 7, 11, 12, 15, and 17

Segmental pigmentation disorder is a type of pigmentary mosaicism consisting of hypopigmented or hyperpigmented patches with midline demarcation and feathery borders that may mimic a large cafe au lait, which typically is oval with smooth borders. This photo is of a patient with segmental pigmentation disorder. Children with segmental pigmentation disorder usually do not have associated developmental abnormalities and this type of pigmentary mosaicism is much more common than McCune Albright syndrome. (Photograph courtesy of Marcia Hogeling, MD.)

Diagnosis

The diagnosis of CALMs is usually established clinically. The differential diagnosis includes the following conditions:

• lentigo

• Becker nevus

• segmental pigmentation disorder, pigmentary mosaicism

• nevus spilus

Congenital Dermal Melanocytosis

Previously referred to as “Mongolian spots,” these blue-gray patches are caused by an increased number of melanocytes in the dermis and are more common in infants of Asian or African descent. They can be found in any area of the body but most commonly in the sacrum and buttocks. Congenital dermal melanocytosis is usually an isolated finding that fades over time. However, extensive congenital dermal melanocytosis can be associated with neurometabolic (specifically lysosomal storage) diseases. Documentation of congenital dermal melanocytosis may be helpful not only in monitoring associated diseases but also in clarifying future skin findings if there is suspicion for abuse.

(Source: VisualDx.)

Congenital Melanocytic Nevus

A congenital melanocytic nevus (CMN) is a pigmented lesion comprised of melanocytes. CMN are distinguished from acquired nevi by their presence at birth or shortly thereafter. The clinical appearance is heterogenous; some are macular while others are plaques; they may be one color or have variegated color; and some are smooth while others have a pebbled or cobblestone texture.

(Source: Giant Congenital Nevus. N Engl J Med 2009.)

Classification

Small CMN are estimated to affect 1% of the population whereas large CMN occur in 1 in 20,000 newborns. CNMs are classified according to the projected adult size. The following categorization scheme has been proposed and agreed upon by experts in the field.

Sequelae of CMN

• psychosocial distress

• secondary development of melanoma

• neurocutaneous melanosis or “CMN syndrome”

• overlying skin changes, including proliferative nodules, eczema, and erosions

Melanoma risk

• Risk varies with phenotype.

• Overall risk in small and medium sized nevi is low (<1%).

• CMN >40 cm associated with an additional CMN, risk is 10%-15%.

• One-third of melanoma in patients with CMN is primary central nervous system (CNS) melanoma.

• An abnormal brain MRI in the first year of life is a strong predictor of melanoma.

• Melanoma in the context of CMN is associated with very poor prognosis.

Neurocutaneous Melanosis (NCM) or “CMN Syndrome”

Neurocutaneous melanosis refers to the presence of melanocytes outside of the skin, most notably in the central nervous system. CMN syndrome refers to the association between CMN and extracutaneous findings (e.g., neurologic abnormalities). Although neurocutaneous melanosis refers to the presence of melanocytes in the central nervous system, the term CMN syndrome is more inclusive and accounts for extracutaneous nonmelanotic CNS abnormalities (e.g., cortical dysplasia and meningioma).

• Risk factors for neurocutaneous melanosis include:

  • CMN >40 cm

  • posterior axial location

  • multiple satellite nevi

  • >2 medium CMN

• Symptoms include seizures, signs of increased intracranial pressure, and developmental delay.

• Symptomatic NCM is associated with poor prognosis and early death.

A 28-year-old male with a giant congenital melanocytic nevus was found to have a melanocytic neoplasm in his left frontoparietal lobe.(Source: Congenital Melanocytic Nevus. N Engl J Med 2013.)

Workup

MRI: Consider an MRI in the following circumstances (ideally within the first 6 months of life, before nerves are myelinated):

• multiple CMN

• large or giant CMN

• >20 satellite nevi

• CMN located over the posterior axis

• giant size of CMN

Surgery: Indications for surgical removal of CMN (although no evidence indicates that early removal is associated with reduction in risk of melanoma):

• cosmetic removal

• features concerning for malignancy

• location that would make long-term observation difficult

• metastatic melanoma without a known primary melanoma

Acquired Nevi

Acquired nevi are different from CMN in that they appear after infancy. The development of acquired nevi is based on several factors, including genetic predisposition, skin type, and sun exposure. By age 10 years, the average white child has between 15 and 30 nevi and the average African, Asian, or Native American child has between 5 and 10 nevi. A longitudinal study of nevi in children revealed that acquired nevi have a dynamic natural history with new lesions appearing or existing lesions disappearing in childhood and adolescence.

Risk factors:

• sun exposure

• lightly pigmented skin

• family history of nevi

Scalp Nevi

Although scalp nevi can be concerning to families and primary care providers, they are usually a benign finding. They can develop at a young age and serve as an indicator of a higher nevus burden. These lesions tend to involute over time. Eclipse nevus and Cockade nevus are two morphologically unique benign nevi that occur on the scalp in children.

Spitz Nevi

A Spitz nevus is a melanocytic lesion that most frequently develops during childhood. It may present as a solitary pink, red, or brown papule most commonly on the face or lower extremity. Spitz nevi tend to demonstrate rapid growth, which may be a concerning feature for patients and providers. Reassuring features include prepubertal age, size <10 mm, symmetry, even distribution of color, and absence of ulceration. Depending on the morphology, these nevi can either be closely monitored or surgically excised.

The lesion is a dome-shaped, pink-red papule. Spitz nevi are frequently nonpigmented. (Photograph courtesy of the Ronald O. Perelman Department of Dermatology, New York University Medical Center).(Source: Melanoma in Children. N Engl J Med 1995.)

Skin Cancer

Malignant melanoma, the deadliest form of skin cancer, is rare in children. Studies suggest that melanoma in patients younger than 20 years accounts for <1% of all melanoma cases. Congenital melanoma is extremely rare, with only a few dozen cases reported in the literature.

Risk factors for pediatric melanoma:

• family history of melanoma

• light skin phenotype

• high nevus count

• congenital melanocytic nevus

• inherited defect of DNA repair

• iatrogenic or acquired immunosuppression

Criteria for recognition of pediatric melanoma:

Pediatric melanomas are often misdiagnosed as benign lesions (66% in a retrospective study at the Mayo Clinic). In children younger than 10 years, pediatric melanoma do not tend to follow the conventional ABCD melanoma detection criteria (Asymmetry, Border irregularity, Color variegation, Diameter >6 mm, Evolution). In a recent study, amelanotic presentation of melanomas in children were often initially misdiagnosed as warts, leading to a median delay of 9 months for correct diagnosis. Fatal pediatric melanomas can be of any subtype.

The following modified ABCD criteria might be more appropriate for the recognition of melanoma in children:

• Amelanotic

• Bleeding, bumps

• Color uniformity

• De novo development, variable diameter

Invasive melanoma (Panel A): amelanotic melanoma may appear to be similar to many common benign skin lesions (e.g., pyogenic granulomas [Panel C], angiomas [Panel D], and dermal nevi [Panel E]).(Source: Red Melanoma. N Engl J Med 2013.)