Pediatric Dermatology- Pigmented Lesions

OPTI-West/Western University of Health Sciences- Silver Falls Dermatology Presenters: Bryce Lynn Desmond, DO; Ben Perry, DO Contributions from: Lauren Boudreaux, DO; Stephanie Howerter, DO; Collin Blattner, DO; Karsten Johnson, DO Disclosures

• We have no financial or conflicts of interest to report Melanocyte Basic Science

• Neural crest origin • Migrate to epidermis, dermis, leptomeninges, retina, choroid, iris, mucous membrane epithelium, inner ear, cochlea, vestibular system • Embryology • First appearance at the end of the 1st trimester • Able to synthesize melanin at the beginning of the 2nd trimester • Ratio of melanocytes to basal cells is 1:10 in skin and 1:4 in hair • Equal numbers of melanocytes across different races • Type, number, size, dispersion, and degree of melanization of the melanosomes determines pigmentation Nevus of Ota

• A.k.a. Nevus Fuscocoeruleus Ophthalmomaxillaris • Onset at birth (50-60%) or 2nd decade • Larger than mongolian spot, does not typically regress spontaneously • Often first 2 branches of trigeminal nerve • Other involved sites include ipsilateral sclera (~66%), tympanum (55%), nasal mucosa (30%). • ~50 cases of melanoma reported • Reported rates of malignant transformation, 0.5%-25% in Asian populations • Ocular melanoma of choroid, orbit, chiasma, meninges have been observed in patients with clinical ocular hyperpigmentation. • Acquired variation seen in primarily Chinese or Japanese adults is called Hori’s nevus • Tx: Q-switched ruby, alexandrite, and Nd:Yag lasers Congenital dermal melanocytosis

• AKA: Mongolian Spot • Usually apparent at birth or within the first few weeks of life • Regresses in >95% by age 18 years; more likely to persist in extensive or extra-sacral variants; most common in Asians and blacks • Presents as a single or multiple, blue-gray patch(es) with indefinite borders; favors the lumbosacral area and buttocks > back • Varies in size from a 2-20+ cm • CALM and melanocytic nevi within Mongolian spots often have a ‘halo’ that lacks dermal melanocytes • DDx: ecchymosis, child abuse, patch blue nevus, venous malformation • Extensive lesions with phakomatosis pigmentovascularis (type 2, 4 , or 5) Nevus Fuscocaeruleus Acromiodeltoideus • AKA: Nevus of Ito • Bimodal age of onset: • 50–60% present at birth or before 1 year of age • 40–50% appear at or around puberty • All persist lifelong • More common in Asians and African Americans; females > males • Involves areas of skin innervated by the posterior supraclavicular and lateral brachiocutaneous nerves • Typically unilateral Café-au-Lait Macule (CALM)

• Light to dark brown macule or patch • 10-20% of normal population can have a single lesion • Generally 2-5 cm in diameter • Conditions associated: • Neurofibromatosis • McCune-Albright syndrome (coast of Maine) • Legius syndrome • Noonan syndrome • LEOPARD syndrome • Fanconi anemia • Bloom syndrome • Ataxia telangiectasia • Tuberous sclerosis • MEN 1 and 2B • Piebaldism • More…… Ephelides

• Light brown macules in sun- exposed areas • Onset typically within first 3 years of age • If acquired after this, can be a marker for UV-induced damage • Histo: NORMAL # of melanocytes, INCREASED pigment in keratinocytes Lentigo Simplex and Oral Melanotic Macules

• Lentigo simplex • Common in younger patients • Increased numbers in childhood or puberty • Sometimes eruptive → lentiginosis • Not related to sun exposure • Oral melanotic macules • Primarily in adults over 40 • Multiple lentigines seen in association with several genetic disorders: • LEOPARD syndrome • Carney complex • Tay syndrome • Pipkin syndrome • Cronkite-Canada syndrome • Bannayan-Riley Ruvalcaba syndrome • Cowden’s disease • Peutz-Jeghers syndrome • Laugier-Hunziker syndrome • More…. LEOPARD syndrome Gene: PTPN11 , AD • Lentigines • ECG abnormalities • Ocular hypertelorism • Pulmonary Stenosis • Abnormal genitalia • Retardation of growth • Deafness • *** LEOPARD Syndrome has no mucosal involvement LEOPARD syndrome Noonan Syndrome AD, PTPN11 • Wide set ears • Ulerythema ophryogenes (keratosis pilaris rubra atrophicans faciei) • Webbed neck • Undescended testes • Low posterior neck hairline • Pulmonary stenosis • Lymphedema • Keloid formation • CALMs CARNEY Complex

NAME LAMB • Nevi • Lentigines • Atrial myxoma • Most common on lips, face, sclera and vulva. • Myxomas (myxoid tumors) • Atrial myxomas • Tumors of heart tissue, often originate in atria • Ephelides & Endocrine • May obstruct blood flow through the heart → • Sertoli tumors fainting, shortness of breath, chest pain • Psammomatous melanotic • Mucocutaneous myxomas schwannomas • Papules or nodules • Pigmented pituitary adenomas • Various anatomic sites: breasts, shoulders, oral • Cushingoid features mucosa and tongue. • Blue nevi – can be found anywhere on body CARNEY complex

AD inheritance • PRKAR1A gene • Encodes the type 1A regulatory subunit of protein kinase A • Cell cycle regulation, growth, and/or proliferation. • Referral to cardiology and endocrinology Peutz-Jeghers

AD, STK11/LKB1 gene mutation (Encodes serine-threonine kinase tumor suppressor)

• Mucocutaneous melanotic macules • Onset before age 5, often fades after puberty • Mouth • Lips • Buccal mucosa • Gingiva • Tongue • Eyes • Palmoplantar • Anogenital Peutz-Jeghers

• Hamartomatous polyps • Bleeding • Intussusception (50%) • Increased incidence of malignancy • 47% mortality rate from cancer by 57 yrs of age • GI adenocarcinoma • Colorectal- 39%, Stomach- 29% • Colonoscopy, upper endoscopy q2-3 yrs beginning in late teens • Breast cancer • Female incidence 45-50% • Mammogram and breast MRI yearly starting at age 25 • Pancreatic cancer • MRCP q1-2 years starting at age 25 to 30 • Ovarian, uterine, cervical, testicular cancer Laugier-Hunziker Syndrome

Sporadic inheritence • Mucocutaneous melanotic macules • Oral: Buccal, lip, tongue, gingiva • Melanonychia • Longitudinal • Half • Complete • Genital melanosis • Neck • Trunk • Palmplantar • Cutaneous pigmentation may fade over time, oral pigmentation often permanent • No increased risk of cancer • Dx of exclusion • R/o Peutz-Jeghers, Addison’s disease, SLE Bannayan-Riley Ruvalcaba AD, PTEN mutation • Allelic to Cowden’s syndrome • Genital Lentigines (penile > vulvar) • Macrocephaly • Intestinal polyposis • Lipomas • Hemangiomas • Scoliosis • Mental retardation Spitz Nevus

• 2 mm to >2 cm well-circumscribed, dome- shaped, red or pigmented papule or nodule • Comprises ~1% of excised melanocytic lesions • Typically children or young adults (<40 yrs) • Majority are acquired, up to 7% congenital • M/c on the head or neck • Histologically can mimic melanoma • Differentiate with S100A6, Ki-67, P16 Spitz Nevus

• Pathogenesis • No particular etiologic factors have been identified to correspond with Spitz nevi • Widespread eruptive Spitz nevi have been associated with many of the same triggers as for common nevi: • HIV infection • Addison’s disease • Chemotherapy • Pregnancy • Puberty • Trauma • Spitz nevi with pregnancy and puberty • Possible hormonally-activated dormant nevi • Atypical spitz nevus risk factors for metastasis: Ulceration, ↑ Breslow depth, atypical mitoses, H-RAS mutation • Treatment: Full-thickness excision Nevus Spilus (Speckled lentiginous nevus)

• Tan patch containing brown macules that develop over time • Can contain atypical nevi and small and medium-sized congenital nevi • Typically larger nevus spilus • No gender predilection • Small risk of cutaneous melanoma Clinical Features and Associations

• More common on the trunk and extremities • Tan patch persists, central nevi increase over time • Cutaneous melanoma arising within a nevus spilus has been reported • Associated syndromes involving nevus spilus include • Phakomatosis pigmentovascularis types III and IV • Phakomatosis pigmentokeratotica • “Speckled lentiginous nevus syndrome” • Ipsilateral dysesthesia, muscular weakness or hyperhidrosis in patients with nevus spilus Halo Nevus (Sutton’s)

• Nevus with peripheral white halo • Epidemiology • Most common in teenagers with multiple nevi • Mean age is 15 years • Typically appears on the back • No Gender predilection • Pathogenesis • Development thought to involve either: 1. An immune response against dysplastic nevus cells with tumor progression • This theory is not supported by histologic evaluations 2. An autoimmune (cell-mediated and/or humoral) reaction against non-specifically altered nevomelanocytes, such as in vitiligo. • The now favored hypothesis Halo Nevus (Sutton’s)

• May have underlying vitiligo (~20%) • Can occur in the setting of melanoma (local or elsewhere) • More common in adults • Can develop in association with sunburn • Histopathology • Residual melanocytes with heavy infiltration of lymphocytes and histiocytes • Management • Full skin examination to r/o melanoma and vitiligo Melanoma

• Malignant tumor that arises from melanocytes • Leading cause of skin cancer death • Incidence rates of melanoma have increased over the past four decades by three- to five-fold • Mortality rates began to stabilize in the early 1990s • Rare in pediatric population • However, 3% of all pediatric cancers are melanoma • The annual transformation rate of a single mole into melanoma is estimated at ≤0.0005% for individuals younger than 40 years. • Misdiagnosed in pediatric population 40% of the time • Prepubescent patients tend to have thicker lesions, can be difficult to distinguish from atypical Spitz nevi histologically • Favorable prognosis compared to adults • Age is a more important prognostic factor for pediatric patients than sentinel lymph node positivity

Becker’s Nevus

• Acquired, unilateral hyperpigmentation +/- underlying smooth muscle • Usually involving the upper trunk of adolescent males • Occasionally may present earlier in life on extremities • Etiology is unknown, but the lesion is associated with a localized increase in androgen receptors • No malignant transformation • Becker’s Nevus Syndrome • Becker’s nevus with unilateral breast and areolar hypoplasia, focal acne, pectus carinatum, limb asymmetry, and spina bifida, scoliosis • Evaluate for musculoskeletal dysfunction with referral as needed • Histopathology • Epidermal thickening, elongation of the rete ridges, and hyperpigmentation of the basal layer with increased melanocytes Blue Nevus

• Blue to blue–black firm papule, nodule or plaques, often with an onset during childhood or adolescence • Aggregates of dermal, dendritic, heavily pigmented melanocytes • Approximately 50% are found on the dorsal aspect of the hands and feet, with the face and scalp being other common sites • Somatic activating mutations in GNA11 and GNAQ (primarily the latter) have been detected in 65–75% of blue nevi References

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Thank you to our residency program for their support and contributions!