Will my child get cancer? It’s important to work with your doctor to perform routine monitoring for this to ensure the best possible outcome. Will my future children get this disease? Your doctor may recommend that you meet with a genetic counselor to discuss the risk of passing this along to your children. This risk can be up to 75% in some cases. Will future-affected children have the same severity of disease? As emphasized above, it is impossible to predict the severity of NF in future children because of the wide variability in symptoms. 15.2. Inguinal freckling “Crowe sign.” 15.3. Café au lait macules. If my child has a large CALM, do I need to worry about MAS or other systemic conditions. Most of the time CALMs occur as an isolated finding, but a careful physical examination, review of systems, and screening laboratory evaluation should be completed. 15.4. 0.2 mm malignant melanoma. 15.5. 0.2 mm malignant melanoma, dermatoscopic view.
CHAPTER
15
BROWN SPOTS
Neurofibromatosis (I/II)
Synonyms
Von Recklinghausen disease, bilateral acoustic schwannomas, NF1, and NF2.
Inheritance
Autosomal dominant and up to 50% represent de novo mutations.
Prenatal Diagnosis
Not commonly tested for; options include chorionic villus sampling, magnetic resonance imaging (MRI), and sonography.
Incidence
NF1 occurs in approximately 1 in 2,500 to 3,000 births and is the most common form (96% of cases); NF2 is about 3% of cases, estimated incidence of 1 in 25,000 births.
Age at Presentation
Findings present with time, about 30% of NF1 patients will meet criteria by age 1 and 97% will meet criteria by age 8; patients with NF2 typically present around the age of 20.
Pathogenesis
NF1 is caused by a mutation in neurofibromin, a tumor suppressor gene; the extent of associated mutations probably affects the severity of phenotypic expression. NF2 is caused by a mutation in the protein merlin/schwannomin, also a tumor suppressor gene.
Key Features
Differential Diagnosis
Segmental neurofibromatosis, CALMs, Legius syndrome, McCune-Albright syndrome, acoustic neuromas, Watson syndrome, tuberous sclerosis, Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Noonan syndrome, Russell-Silver syndrome, LEOPARD syndrome, and urticaria pigmentosa.
Laboratory Data
Neurofibromatosis is a clinical diagnosis with no lab monitoring guidelines; in patients who do not meet clinical criteria, yet suspicions are high, genetic testing may be helpful; urinary free catecholamines and their metabolites measured in a 24-hour urine collection may be used to screen for pheochromocytoma.
Management
Management consists of monitoring for serious complications associated with the syndrome and will vary depending on patient age
Prognosis
NF1 is likely associated with increased mortality; mean age of death ~54.4 years old compared with 70.1 years old in general population; also ~1.2 times more likely to have a malignant neoplasm of any type (much higher in younger patients); 5 to 6 times more likely to die from a malignant neoplasm; vascular diseases are also significantly more likely to be fatal in patients <30 years of age with NF1.
PEARL/WHAT PARENTS ASK
Skin
|
Associated Findings 
McCune-Albright Syndrome
Synonyms
Albright syndrome, polyostotic fibrous dysplasia, precocious puberty with polyostotic fibrosis and abnormal pigmentation, and osteitis fibrosa disseminate.
Inheritance
Sporadic
Prenatal Diagnosis
n/a
Incidence
Unknown, very rare. Prevalence 1 in 100,000 to 1,000,000 live births.
Age at Presentation
Early childhood, average age ~5 years but earlier for girls. Overall F>M 2:1. If severe, then endocrine problems may appear as early as neonatal period.
Pathogenesis
Sporadic, post-zygotic, random, somatic activating mutation in GNAS1 gene; results in genetic mosaicism not involving germline so is not vertically transmitted; encodes a G protein involved in coupling cell surface receptors with intracellular proteins in signaling pathways associated with the development of the clinical signs seen in MAS.
Key Features
Differential Diagnosis
Neurofibromatosis types 1 and 2, pituitary tumors, multiple endocrine neoplasia types 1 and 2, acromegaly, Fanconi anemia, adrenal tumors, Grave disease, and tuberous sclerosis.
Laboratory Data
Management
Pediatric endocrine consultation: Long-term treatment with bisphosphonates may be beneficial for bony disease.Pediatric orthopedic surgeon experienced in PFD management.
Prognosis
Rare cases of malignancy are reported in skeletal lesions, life expectancy is still close to normal, overall prognosis is variable based on the severity of an individual patient’s manifestations.
PEARL/WHAT PARENTS ASK
Skin
|
Associated Findings 
Malignant Melanoma
Synonyms
Pediatric melanoma and adolescent and young adult melanoma.
Inheritance
Usually acquired; if genetic, associated with Familial Melanoma syndrome (autosomal dominant).
Prenatal Diagnosis
n/a
Incidence
1.1 cases per million in children age 1 to 4 years; 10.4 per million in age 15 to 29 years.
Age at Presentation
While rare, malignant melanoma is the most common skin cancer in children; melanoma can appear at any age, but age 15 to 19 years are 10 times more frequent than in age 5 to 9 years; children with 100+ nevi are also at higher risk.
Pathogenesis
Malignant transformation of melanocytes via multiple factors including UV-induced DNA damage, preexisting genetic susceptibility (CDKN2A and CDK4 mutations in familial melanoma and BRAF and NRAS mutations in conventional melanoma and congenital melanocytic nevi) and other, undefined triggers; majority are sporadic and likely triggered by UV-associated damage; indoor tanning leads to a significant increase in melanoma risk.
Key Features
Three typical patterns; if age <10 years, lesion site equally distributed on body; age >10 years, then more often see truncal lesions; face and trunk more common in males; extremity lesions more common in females; ocular melanoma rare.
Differential Diagnosis
Nevi, dysplastic/atypical nevi, congenital melanocytic nevi, halo nevi, Spitz nevi.
Laboratory Data
Full-thickness biopsy of suspicious appearing lesions, gold standard to confirm diagnosis and measure Breslow depth; excisional biopsy ideal, punch biopsy acceptable for small lesions, avoid shave biopsy as it can lead to inadequate sample and erroneous measurement of Breslow depth; sentinel lymph node biopsy may be done for thicker lesions for staging and prognostic purposes; TNM criteria for staging same as for adults.
Management
Prognosis
Based on stage per American Joint Committee on Cancer, Breslow depth remains single-most important prognostic indicator; whereas pediatric melanoma is not necessarily more aggressive than adult disease, it may often not be detected until it is at a more advanced stage; children generally have a better prognosis than adults. Prognosis in children of color is not as good as lighter-pigmented children probably because of a delay in diagnosis and removal. 
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