AAD San Diego S021 2018 Skin Tumors in Children Jane M. Grant-Kels, MD,FAAD grant@uchc.edu Founding Chair Emeritus, Derm Dept, UCONN Vice Chair Dept of Dermatology Professor of Dermatology, Pathology and Pediatrics Director of Cutaneous Oncology Ctr & Program LaChance, Shahriari, Kerr, Grant-Kels. : Kids are not just little people. Clinics in Dermatology 2016;34:742-748. Waldman, Grant-Kels. Malignant Skin Tumors: Kids are not just little people. Clinics in Dermatology 2017;35:517-529. Conflicts of Interest: None Skin Tumors in Children Skin tumors in kids Vs adults are different re: epidemiology, pathogenesis & Rx In kids can be presenting sign of underlying genetic condition or other serious disease process, BCC, SCC 1. Epidemiology 2. Etiology 3. Clinical presentation 4. Work-up 5. Rx in Children: Epidemiology Children get MM & incidence on the rise 0.7-2% of all MM cases occur in pts < 20 yo Incidence w/ ing age for < 20 yo 2.5% increase per yr in 0-18yo ~1% increase in pre-adol; ~ 3% in adol 5.4 MMs per 1 million children in USA Most common form of skin ca in children Adol pop (11-19 yo): MM behaves ~ adults Pre-adol pop: differences noted Lange, et al. J Clin Oncol 2007;25:1363-8 Neier, et al. J Pediatr Hematol Oncol 2012;34:S51-4 MM % in kids Yrs Old 3.8% 0-4 5.7% 5-9 17.3% 10-14 73.2% 15-19 in Children: Etiology FH of MM or Atypical Mole MM Syndrome Hx of > 3 sunburns Numerous acq d mel nevi Large cong mel nevi Immunosuppression Pre-existing conditions as XP Tanning parlors MM in Children: Clinical Presentation ABCDE only for adults & adol Pre-adolescents 77% Amelanotic flesh colored, pink or red DDx: Warts, PG Single color, not variegated like in adults > 90% (up to 100%) papular or nodular Well circumscribed ~50% are <6mm Head & neck Favor girls Cordoro, et al. JAAD 2013;68:913-25 1
DDx Between Adult & Pre-Adol MMs CLINICAL Pediatric Adult Color Amelanotic Pigmented Morphology Papulonodular Macule, papule or rarely nodule Border Regular Irregular Well circumscribed Diameter 6mm >6mm Body site Head and neck Trunk Gender Females Males ABBCDDE Detection for Pre-Adol MM Amelanotic Bleeding Bumps uniform Color small Diameter De novo development & Evolution DDx Between Adult & Pre Adol MMs PATHOLOGY Histologic Subtypes Pediatric More commonly nodular; SSMM rare (Verzi AE, et al. JAAD 2017;77:886-92) Breslow thickness Thicker at dx (93% >1mm) Role of mitotic rate & ulceration Does not necessarily correlate with worse prognosis Adult Less commonly nodular Thinner at dx Negative prognostic implication STUMP Lesions Spitzoid Tumors of Uncertain Malignant Potential Lead to erroneous classification alter epidemiologic data of pedi MM DO NOT USE SLNB FOR DX IC PURPOSES Molecular markers: HRAS in 4.5-29% of Spitz Vs 0% in Spitzoid MMs BRAF & NRAS more common in MM than Spitz nevi Loss of INK4A gene & gain of c-kit more often in pediatric MMs Comparative genomic hybridization & FISH McCormack, et al. Res 2014;24:437-447 in Children: Work Up Most use AJCC TNM staging system altho not formally recognized for pedi pts SLNB role debated in peds bc more likely to be positive + in 25-40% of pedi MMs Prognostic relevance??? SLNB + described in other benign nevi as blue nevi, cong mel nevi, Spitz nevi, STUMP lesions Indication Prognostic implication Rx: Adult Vs Pedi MMs SLNB Pediatric Adult MM Controversial, more likely to be positive Positivity does not necessarily correlate with worse prognosis MANAGEMENT No completed clinical trials in kids: use adult criteria Excision margins Same as adults Yes Chemotherapy/radia Used less Yes tion Biologics Used more than chemo or rad, esp interferon alfa-2b Useful for staging Positivity confers worse prognosis Yes 2
in Children: Prognosis Majority of pre-adol MMs present at > Stage IIA: Delay in Dx or more locally aggressive tumor? Is pedi MM diff disease than adult MM? Diff molecular markers described Prognosis varied by study: Cordoro, et al. JAAD 2013;68:913-25 Better prognosis despite depth 2 0 to erroneous dx Berk, et al. Pediatr Dermatol 2010;27:244-54 Worse prognosis: 5 yr survival 77% for pre-adol Vs 88% for adol /adults Lange, et al. J Clin Oncol 2007;25:1363-68 No diff than adults Blazer, et al. Semin Oncol 2007;34:270-80 BCC in Children: Epidemiology Rate of 1.9 BCCs per 10,000 pedi derm visits Orozco-Covarrubias, et al. JAAD 1994;30:243-9 >100 cases of de novo pedi BCC reported Griffin, et al. JAAD 2007;57:S97-S102 Older age, blond/red hair, FST I, green/blue eyes, latitude of residence, immunosuppression, predisposing genetic conditions, hx of radiotherapy Pedi cases: no gender predilection Almost always w/ underlying genetic or medical condition BCC in Children: Etiology De novo pedi BCC <10% of all pedi BCC UVL + underlying condition predisposing to BCC BCCs more common in white than AA kids w/ BCNS BCNS, XP, genodermatoses (albinism, Bazex synd) Vitiligo, Nevus sebaceous Transplant immunosuppression (esp heart > kidney) Hx of radiotherapy for malignancy 10 yr latency for kids vs 20 yr for adults Exposure to arsenic, polyaromatic hydrocarbon, etc BCC in Children: Clinical Presentation Nodular BCC- most common Morpheaform & superficial reported Most common on sun exposed areas: 90% of de novo pedi BCC on face Truncal lesions higher lifetime risk of additional BCCs Ear & nose BCC higher recurrence rate Metastasis reported (LN, lung, bone, liver) Griffin, et al. JAAD 2007;57:S97-S102 Genodermatoses Basal Cell Nevus Syndrome BCC in Children: Work Up WU for underlying cause as genetic condition Xeroderma Pigmentosum Oculocutaneous Albinism Characteristics Multiple BCCs, Skeletal Abnormalities, Characteristic Facies, Odontogenic Cysts, Intracranial Calcifications, Intellectual Impairment Multiple BCCs & SCCs, early signs of sun damage (freckling, blistering sunburn, telangiectasias), photophobia, dry skin, irregular skin pigmentation Amelanotic skin, irises, & hair, decreased visual acuity, photophobia BCC in Children: Rx No guidelines in kids but Rx ~ as adults Radiotherapy not recommended due to lifetime risk of subsequent malignancies & cosmesis BCNS: photodynamic Rx Locally advanced or metastatic BCC: hedgehog pathway inhibitors (but not studied in kids) 3
SCC in Children: Epidemiology <1% of all pedi cancers 0.2 cases per 100,000 children per 5yrs Only 6 cases over 28 yrs by UK National Registry of Childhood Tumors No gender predilection All races: most common skin ca in FST IV-VI FST, green/blue eyes, red/blond hair HPV, hx radiorx, immunosuppression (transplant) Burned/scarred skin Chow, et al. J Pediatr Surg 2007;42:2035-9 SCC in Children: Etiology Trigger UVL: cumulative + severity of exposure Altho reported de novo, rarely w/o underlying predisposing condition SCC in Children: Etiology Childhood exposure increase SCC adult risk: Ionizing radiation: intensity + duration Arsenic, polyaromatic hyrdrocarbons; HPV + UVL Chronically inflamed /damaged skin: burns (reported w/ SCC in kids but rare), LSA, DLE, etc Immunosuppression: severity + length SCC in kids rare but reported (lack of cumulative UVL exposure) Immunosuppression + chronic exposure to antifungal voriconazole (photosensitizing) increase SCCs!!! SCC in Children Etiology: Predisposing Genodermatoses XP: 2 0 to UVL + defective pyrimidine dimer repair SCCs start ~ 8yo Oculocutaneous albinism: 2 0 to UVL + no melanin EB: 2 0 to chronic inflamm + UVL Highest in EB recessive dystrophic form TBSE start 10yo as 10% develop SCC by 25yo. 6yo w/ RDEB reported w/ SCC Severe generalized RDEB: ~80% of pts die 2 0 to complications of SCC by 45 yo SCC in Children: Clinical Presentation SCC in Children: Work Up AK & SCC in child presentation ~ adult SCC in chronically injured skin as in EB: more aggressive Rule out underlying predisposing condition if not obvious 4
SCC in Children: Rx When arise in transplant, immunosuppressed or EB pt: Rx aggressively Sunscreens Tumors in Children: Bottom Line Bottom Line Children with skin tumors : look for underlying predisposing genetic or medical condition Prognosis in children can vary from adults Clinical presentation of skin tumors can vary in kids from adults 5