The Diagnostic and Clinical Significance of Café-au-lait Macules
Section snippets
Definition
Café-au-lait, also referred to as café-au-lait spots or café-au-lait macules, present as well-circumscribed, evenly pigmented macules and patches that range in size from 1 to 2 mm to greater than 20 cm in greatest diameter (Fig. 1). In light-skinned persons, the color appears light brown, or “coffee with milk,” whereas in darker-skinned patients the color may appear as a medium to dark brown hue. Morphologically, café-au-lait have often been described as appearing either oval and
Epidemiology and natural history
Solitary café-au-lait are common birthmarks. The presence of more than one café-au-lait, however, is less common. The frequency of multiple lesions, which has significance regarding the requirement for additional evaluation, has been examined in several population-based studies. Overall, the presence of one or more café-au-lait appears more common in African Americans than in Caucasians. The overall prevalence of at least one café-au-lait was noted to be present in 2.5% of neonates among 18,155
Pathogenesis
Although café-au-lait may be seen anywhere on the body, they appear to be most common on the torso and occur rarely on the face, suggesting that sunlight exposure is not involved in the pathogenesis. An increase in the secretion of hepatocyte growth factor (HGF) and stem cell factor (SCF) by dermal fibroblasts has been reported in café-au-lait associated with NF-1, suggesting that these growth factors may be associated with the increased epidermal melanization observed in at least some
Differential diagnosis
Although café-au-lait are usually readily diagnosed on examination, occasionally they may be difficult to differentiate from other pigmented lesions (Table 1). At times, café-au-lait may be difficult to distinguish from other pigmented birthmarks, including congenital melanocytic nevi, speckled lentiginous nevus, Becker nevus, and forms of pigmentary mosaicism such as nevoid hypermelanosisand segmental pigmentation disorder. Acquired pigmentary lesions, including ephelides (freckles), lentigo,
Evaluation
Presentation of a child with café-au-lait macules to the primary care provider, geneticist, or dermatologist is a common scenario. Two prospective cohort studies have attempted to define the predictive value of the number and morphology of café-au-lait macules in children with regard to eventual diagnosis of NF-1 or other disorders associated with café-au-lait. In one study, a cohort of 41 children with 6 or more café-au-lait greater than 5 mm in diameter was followed prospectively.14 The
Clinical presentations
Although neurofibromatosis-1 is the most common and well-recognized syndrome associated with café-au-lait, they have been associated with several other syndromes, including neurofibromatosis-2 (NF-2), McCune-Albright syndrome, and Noonan syndrome. A review of the features of many of the syndromes associated with café-au-lait is presented in Table 2. Although comprehensive, this list is not exhaustive, and for many of these syndromes the evidence that café-au-lait occur with more frequency than
Treatment
Treatment of café-au-lait is not required for medical reasons, but is often requested by patients and caregivers for cosmetic concerns, in particular with large, segmental café-au-lait or when café-au-lait are present on the face. There is no uniformly successful treatment modality for removing café-au-lait. Several medical lasers have been used for the treatment of café-au-lait, all with variable clinical results. Complications of laser surgery include discoloration of the skin and scarring,
Summary
Café-au-lait are common pigmented skin lesions in children. Although most café-au-lait present as 1 or 2 hyperpigmented macules or patches in an otherwise healthy child, the presence of multiple café-au-lait, large segmental café-au-lait, associated facial dysmorphism, other cutaneous anomalies, or unusual findings on physical examination should suggest the possibility of an associated syndrome. While NF-1 is the most common syndrome seen in children with multiple café-au-lait, other syndromes
References (160)
- et al.
Birthmarks with serious medical significance: nevocullular nevi, sebaceous nevi, and multiple café au lait spots
J Pediatr
(1979) - et al.
“Sunburn” freckles, café-au-lait macules, and other pigmented lesions of schoolchildren: the Vancouver Mole Study
J Am Acad Dermatol
(1995) - et al.
The eastern Australian childhood nevus study: prevalence of atypical nevi, congenital nevus-like nevi, and other pigmented lesions
J Am Acad Dermatol
(1995) Melanoma arising in a café au lait spot of neurofibromatosis
Am J Surg
(1957)- et al.
Neurofibromatosis type 1
J Am Acad Dermatol
(2009) Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective
Lancet Neurol
(2007)- et al.
Neurofibromatosis and childhood leukemia
J Pediatr
(1978) - et al.
Rhabdomyosarcoma complicating multiple neurofibromatosis
J Pediatr
(1978) - et al.
von Recklinghausen’s disease and pheochromocytomas
J Urol
(1999) - et al.
A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations
Cell
(1990)
Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus
Cell
Elevated risk for MPNST in NF1 microdeletion patients
Am J Hum Genet
Somatic mutation analysis in NF1 café au lait spots reveals two NF1 hits in the melanocytes
J Invest Dermatol
Bilateral segmental neurofibromatosis: a case report and review
Pediatr Neurol
Bilateral dermatomal neurofibromatosis
J Am Acad Dermatol
A clinical variant of neurofibromatosis type 1: familial spinal neurofibromatosis with a frameshift mutation in the NF1 gene
Am J Hum Genet
NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome
Am J Hum Genet
Pathophysiology of neurofibromatosis. IV. Dermatologic insights into heterogeneity and pathogenesis
J Am Acad Dermatol
Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought
Otol Neurotol
Neurofibromatosis type 2
Lancet
The diagnosis and management of neurofibromatosis 2 in childhood
Semin Pediatr Neurol
Ann Dermatol Venereol
Café-au-lait spots in neurofibromatosis type 1 and in healthy control individuals: hyperpigmentation of a different kind?
Arch Dermatol Res
A cell culture study on melanocytes from patients with neurofibromatosis-1
Arch Dermatol Res
The incidence and significance of birthmarks in a cohort of 4,641 newborns
Pediatr Dermatol
Diagnostic value of the café-au-lait spot in children
Arch Dis Child
Café-au-lait spots in schoolchildren
Arch Dis Child
Frequency of congenital nevi, nevi spili and café-au-lait spots and their relation to nevus count and skin complexion in 939 children
Dermatologica
Von Recklinghausen neurofibromatosis
N Engl J Med
Z Hautkr
Diagnostic outcome in children with multiple café au lait spots
Pediatrics
Relationship between café-au-lait spots as the only symptom and peripheral neurofibromatosis (NF1): a follow-up study
Eur J Pediatr
Predictive value of café au lait macules at initial consultation in the diagnosis of neurofibromatosis type 1
Arch Dermatol
Diagnostic importance of café-au-lait spot in neurofibromatosis
AMA Arch Intern Med
The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2
JAMA
Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference
Arch Neurol
Optic pathway gliomas in neurofibromatosis-1: controversies and recommendations
Ann Neurol
Optic pathway gliomas in children with neurofibromatosis 1: consensus statement from the NF1 optic pathway glioma task force
Ann Neurol
Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children
Pediatrics
Neurofibromatosis-1 in childhood
Adv Dermatol
Neurofibromatosis type 1 revisited
Pediatrics
The diagnosis of neurofibromatosis-1 in the child under the age of 6 years
Am J Dis Child
Neurofibromas in children with neurofibromatosis 1
J Child Neurol
CT imaging in adults with neurofibromatosis-1: frequent asymptomatic plexiform lesions
Neurology
Malignant peripheral nerve sheath tumours in neurofibromatosis 1
J Med Genet
Juvenile xanthogranuloma, neurofibromatosis 1, and juvenile chronic myeloid leukemia
Arch Dermatol
Juvenile xanthogranuloma, neurofibromatosis, and juvenile chronic myelogenous leukemia. World statistical analysis
Arch Dermatol
Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1
Neurology
Neurofibromatosis type 1 and childhood cancer
Cancer
Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases
Am J Surg Pathol
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Disclosure: The author has nothing to disclose.