Dermoscopy of Melanocytic Lesions in Children

Alexander C. Katoulis Assoc. Professor of and Venereology

2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens, Medical School, “Attikon” General University Hospital

19th Annual Meeting of the European Society for Pediatric Dermatology, Dubrovnic, Croatia, May 4, 2019 Disclosure of conflicts of interest & relationships with industry

Prof. Alexander C. Katoulis, MD, PhD

I have no conflicts of interest to declare

I do not have any relevant relationships with industry Dermoscopy

 In vivo, non-invasive diagnostic technique  Light source (polarized or non-polarized) + magnifying lens (x10)  Enables visualization of patterns, structures and colors  Bridge between clinical examination and histopathology  Improves diagnostic accuracy by 30%  Needs training and experience DERMOSCOPY: GENERAL CONSIDERATIONS Dermoscopy for melanocytic lesions  Improves diagnostic accuracy  Improves both sensitivity and specificity  Better detection of  Fewer unnecessary biopsies or excisions  Dermoscopy can pick out the few malignant lesions out of a huge number of benign lesions

BENIGN LESIONS (NEVI) MALIGNANT LESIONS () Melanocytic lesions in children  Cause particular concern to parents  30% of pediatric dermatologic consultations are due to concerns regarding nevi (Aguillera P et al, 2009)  Concern is - disproportionate to the rare occurrence of pediatric melanoma - proportionate to the impact of a possible melanoma diagnosis in a child Dermoscopy in children  It is the ideal tool for examining children  Painless  No special examining conditions necessary  Sometimes its shape and light are even amusing for children Melanocytic lesions in children

Benign Malignant  Congenital nevi  Malignant melanoma  Blue  Spitzoid melanoma  Acquired common and dysplastic nevi   Special types (irritated, recurring, combined)  Special sites Diagnostic procedure

 History (personal, family)  Asseement of risk factors  History of the lesion  Clinical examination  Dermoscopy  Other skin imaging techniques  Histopathology= gold standard for definite diagnosis Main diagnostic algorithm: two steps Dermoscopic evaluation of a lesion • Dermoscopic features of melanocytic lesion: present YES or NO? Pigment network, globules, dots, radial streaks, pseudopods, blotch, regression, blue white, veil

• Symmetry: YES or NO • Color: ONE or MORE • Pattern analysis: - Global pattern - Local dermoscopic features - Additional dermoscopic features: vessels, etc - Confounding features: scales, crusts, hair, etc.

DERMOSCOPIC DIAGNOSIS

DECISION: Excision – Follow up – No action Haliasos EC et al, Pediatr Dermatol 2013 Haliasos EC et al, Pediatr Dermatol 2013 Haliasos EC et al, Pediatr Dermatol 2013 Melanoma-specific dermoscopic criteria

 Dermoscopic features  Atypical network associated with MM  Atypical globules and dots  No one is pathognomic  Blotch/eccentric  Their presence raise hyperpigmented area suspicion of MM  Blue-white structures  Concurrent evaluation of (elevated part) history, clinical and  Regression (flat part) dermoscopic findings lead  Reticular depigmentation to dermoscopic diagnosis and management decision  Polymorphous vessels  Crystalline structures HISTOPATHOLOGIC CORRELATES OF DERMOSCOPIC-SPECIFIC STRUCTURES HISTOPATHOLOGIC CORRELATES OF DERMOSCOPIC-SPECIFIC STRUCTURES

Haliasos EC et al, Pediatr Dermatol 2013 If there is: -Asymmetry - Multiple colors - Global pattern does not conform to a benign pattern - Lesion reveals any of the melanoma-specific structures

OR If a dermoscopic diagnosis of a benign lesion can not be made with confidence

The lesion is suspicious and a biopsy should be performed DERMOSCOPY OF MELANOCYTIC LESIONS CONGENITAL MELANOCYTIC NEVI Congenital melanocytic nevi (CMN)  Nevi present at birth or appearing within the first year of life (tardive)  Persist throughout all life  Result from errors in migration and proliferation of melanocytic progenitor cells during embryogenesis  Are found in 1-6% of newborns (0.5-31.7%) (Price HN, Schaffer JV, 2010)  Estimated incidence for giant CMN: 1 in 20,000- 500,000 live births Alikhan A et al, 2012 Clinical characteristics  Flat or raised with well-demarcated borders  Smooth, papillomatous or verrucous surface  Light- to dark-brown color, variegation of color  Often numerous terminal hair  Over time may show variations in color, borders, and surface  Giant CMN often have scattered smaller satellite CMN (Marghoob AA, 2002) Congenital Congenital melanocytic nevus (medium) Giant congenital melanocytic nevus

Courtesy of Dr Vincenzo Piccolo, Naples, Italy Congenital melanocytic nevi (CMN)  CMN are usually classified according to size* into: small (<1.5 cm), medium (1.5–20 cm), large (>20-40 cm), and giant or “garment” (≥40 cm) (Alikhan A et al, 2012)  Patients with giant CMN and many satellite nevi are at greatest risk of developing cutaneous and extracutaneous melanoma and neurocutaneous melanocytosis

* Projected adult size Dermoscopy of CMN

Global pattern Local features  Cobblestone (large  Globules (regular, angulated globules)/ irregular) globular (head and  Dots trunk)  Pigment network  Reticular (lower (regular, irregular) extremities)  Multifocal perifolicular hypopigmentation  Homogeneous  Hyperpigmented zones  Multicomponent () Dermoscopy of CMN

Additional features Confounding features  Vessels (in up to 70%):  Hair comma vessels, dotted  Milia-like cysts vessels, serpentine  Comedo-like openings (Haliasos EC et al, 2012) Cobblestone/globular pattern Hair Multicomponent pattern Perifollicular hypopigmentation Zones of hyperpigmentation (pseudomelanoma) Risk of melanoma development  There is lack of consensus  In studies, varies between 0.05% and 10.7%  Depends mostly on: - size of the nevus - age of the patient  In 6571 patients followed for mean 3.4-23.7 years, only 0.7% developed melanoma (median age at diagnosis 7 years, highest risk for giant CMN) (Krengel S et al, 2006) Melanoma arising in a small/medium CMN  Low risk for small/medium CMN  Lifetime risk estimated to be up to 1%  Risk seems to be related to age: 0.7 per million for children < 10 years – 13.2 per million for adolescents 15-19 years  MM tend to develop: - later in life (after childhood) - at the dermo-epidermal junction with SSM histology (Moscarella E et al, 2013) Dermoscopy can help in the early detection: appearance of new dermoscopic structures at the periphery of the lesion Melanoma arising in a small/medium CMN

Haliasos EC et al, Pediatr Dermatol 2013 Melanoma arising in a small/medium CMN Melanoma arising in a CMN of a 14 years old child

Courtesy of Dr Vincenzo Piccolo, Naples, Italy Melanoma arising in a CMN of a 11 years old child

Courtesy of Dr Vincenzo Piccolo, Naples, Italy Melanoma arising in a large/giant CMN

 MM tends to develop: ❖ earlier in life - 1/3 of MM under 12 years is related to the presence of giant CMN (Bonifaci E et al, 2001) - risk is highest for giant CMN during childhood (Krengel S et al, 2006) ❖ deeper, below the dermo-epidermal junction with histology (Marghoob AA, 2002)  Clinically, is characterized by a growing nodule within the CMN  Dermoscopically, features of intermediate/thick MM: blotch, blue-white veil, blue and black color, crystalline structures

Dermoscopy cannot be relied upon for early identification Management  Individualized to address risk for MM and aesthetic – psychosocial issues  For small/medium CMN: early excision or regular clinical and dermoscopic follow up ± digital dermoscopy, yearly  For large CMN: prophylactic early excision + follow up (for MM development outside of the nevus) Moscarella E et al, 2013 Nevus spilus Nevus spilus  Hyperpigmented patch studded with numerous macules and papules  Speckled appearance  Usually evident at birth  Superficial variant of CMN  Two subtypes: macular and papular Nevus spilus maculosus and papulosus  Macular type: dark flat speckles evenly distributed on a light brown background (“polka-dot pattern” or “star map”)  Papular type: speckles usually represent dermal melanocytic nevi or small CMN  Occasionally, other AMN, Spitz nevi, blue nevi, and melanoma may arise (Cramer SF, 2001)

Vidaurri-de la Cruz H, Hapel R, 2006 Dermoscopy of nevus spilus  Homogeneous tan or a faint network as a background  Dark brown or pink macules and papules within the nevus spilus with dermoscopic features corresponding to the type of nevus (Zalaudek I et al, 2006)  Global pattern: homogeneous, reticular, globular or multi-component  Local features: - macular speckles exhibit a reticular pattern - papular speckles manifest a globular pattern Nevus spilus Nevus spilus Malignant potential of nevus spilus

 The risk varies in the literature  MM reported more commonly in the macular subtype (25% vs 10%)  Propensity to develop Spitz nevi appears to be equal for both types Vidaurri-de la Cruz H, Hapel R, 2006; Hapel R, 2009 arising in a nevus spilus ACQUIRED MELANOCYTIC NEVI Acquired melanocytic nevi (AMN)  Appear in early childhood and increase in numbers during adolescence (Stinco G et al, 2011)  AMN are classified into: - common (junctional, dermal, compound) - atypical or dysplastic Common acquired melanocytic nevi

Clinical characteristics Dermoscopic features ◼ Flat or slightly raised ◼ Global pattern (no ◼ Up to 5mm more than one): reticular, globular, ◼ Regular border homogenous ◼ Symmetry of shape ◼ Local features: regular ◼ 1-2 colors (brown, network, dots, globules black) ◼ Additional features: none ◼ Symmetry (in structure) Common AMN: reticular and homogeneous pattern Common AMN: globular pattern Papillomatous dermal nevi (Unna type)

Clinical characteristics Dermoscopic features ◼ Soft ◼ Global pattern: globular, cobblestone, homogenous, ◼ Pedunculated or sessile non specific, or ◼ Papillomatous surface combination of two ◼ Tan or brown color ◼ Local features: exophytic papillomatous structures ◼ Trunk, extremities ◼ Additional features: comma vessels,milia-like cysts, comedo-like openings ◼ Other: hair Papillomatous dermal nevi (Unna type) Papillomatous dermal nevi (Unna type)

Exophytic papillomatous structures Papillomatous dermal nevi (Unna type)

Comma vessels Papillomatous dermal nevi (Unna type): globular pattern Dermal nevi of the face (Miescher type)

Clinical characteristics ◼ Dome-shaped nodule ◼ Tan to light brown Dermal nevi of the face (Miescher type) Dermoscopic features ◼ Global pattern: pseudo- pigment network, homogenous, non specific ◼ Local features: comma vessels ◼ Additional features: milia-like cysts, comedo-like openings, hair Dermal nevi of the face (Miescher type): pseudonetwork Dysplastic nevi (Clark) Clinical characteristics ◼ Usuall arise after puberty ◼ Irregular border ◼ Color variability with various shades of brown ◼ Diameter > 5 mm ◼ Flat or elevated (papule in the center, macule in the periphery) ◼ Trunk, extremities ◼ Atypical mole syndrome (familial or sporadic): > 20 DMN, ◼ Risk factor (marker) and precursor lesion (?) for MM Dysplastic nevi (Clark) Dysplastic nevi Dysplastic nevi (Clark) Dermoscopic features ◼ Global pattern: reticular, globular, homogenous, combination of 2, multi-component (!!!) ◼ Local features: melanocytic lesion criteria (no one specific) ◼ Additional features: melanoma-specific criteria (blotch, streaks, blue-white veil, dotted vessels) Dysplastic nevi (Clark) Dysplastic nevi (Clark)

Dermoscopic categories ◼ Nevus with central hypopigmentation ◼ Nevus with central hyperpigmentation ◼ Nevus with multi-focal hyper-/hypo-pigmentation ◼ Nevus with eccentric hyperpigmentation DMN with central hypopigmentation (“fried egg”) DMN with central hyperpigmentation («black nevus») DMN with multifocal hyperpigmentation DMN with eccentric hyperpigmentation DMN with eccentric and multifocal hyperpigmentation DMN with atypical network Dysplastic nevi (Clark)

◼ Often difficult to differentiate from early MM or MM in situ ◼ A gray zone exists ◼ Special attention to “DMN”: ❖ with a multi-component pattern ❖ eccentric hyperpigmentation ❖ eccentric hypopigmentation (regression) ❖ Atypical network

Short-term follow-up (3 months) or Excision Management of dysplastic nevi Due to the risk for MM development:  Regular follow up (clinical examination and dermoscopy)  Preferably with digital dermoscopy  Frequency: every 6-12 months depending on the risk factors that are present  Excision is recommended only for suspect lesions  Prophylactic excision does not lower the future risk (most MM arise de novo)  Avoid unnecessarary excisions especially in children Growing AMN  Common in children and adolescents  Distinct pattern of globules surrounding the entire perimeter of the nevus  Globules correspond to nevomelanocytic nests at the tips of rete ridges (Xu J et al, 2009)  Results in a symmetric enlargement  Progressively the peripheral globules become sparser and disappear and the nevus assumes a reticular or homogeneous pattern  Changing lesions with symmetric peripheral globular pattern in children are benign and do not require biopsy (Zalaudek I et al, 2011) Growing AMN Growing AMN: peripheral globular pattern

Haliasos EC et al, Pediatr Dermatol 2013 Blue nevi (BN)  Benign neoplasms of dermal melanocytes  Result from an arrest in melanocytes migration to the DEJ during fetal development  Appear during childhood or adolescence  Remain stable throughout life Blue nevi (BN) Clinical variants  Common BN: - blue-gray/brown /black - macule or dome-shaped papule, distinct borders - <1 cm - head, neck, sacrum, dorsa of the hands and feet (50%)  Cellular BN: - blue to black nodules - 1 to 3 cm - buttocks or sacrum, also scalp, face, and feet (premalignant) Blue nevus Dermoscopy of blue nevi  Global pattern: homogeneous (bluish color)  Local and additional features: none Bluish diffuse pigmentation + Absence of other dermoscopic structures + Sharp demarcation

Accurate recognition of BN

 Presence of dermoscopic structures or multiple colors → suspicion of cellular BN or MM  Addition of a whitish hue → fibrosis in aging BN Common blue nevus Common blue nevus Common blue nevus Fibrosis in aging blue nevus Cellular blue nevus Cellular blue nevus HALO NEVUS (SUTTON) Halo nevus (Sutton)  Benign MN with a peripheral zone of depigmentation  More common in children and young adults  Prevalence ~1%  Single or multiple lesions  Most often on the trunk (back)  Result of an immune-mediated reaction in four stages (Zeff RA et al, 1997): white peripheral halo → involution of the central nevus → disappearance of nevus → repigmentation to normal skin color  HN followed with digital dermoscopy: 51.5% decrease in halo size, 27.3% enlargement (Kolm I et al, 2006)  Association with autoimmune diseases (vitiligo) Halo nevus Halo nevus Halo nevus (Sutton)  The vast majority of HN are benign Attention!!!  Single lesion - leukoderma can develop around a MM - always evaluate carefully a pigmented lesion surrounded by a depigmented halo (especially in adults)  Multiple lesions - although it is common and suggests begninity, the sudden appearance of multiple HN can be associated with MM (Schaffer JV, 2007) Dermoscopy of halo nevus  Approximately 80%: - globular or homogeneous pattern in the center of the lesion, with - surrounding halo of depigmentation  In completely regressed HN: - light brown or pink central area with dotted vessels  Global pattern: homogenous, globular, reticular  Local features: none specific  Additional features: white halo Halo nevus Halo nevus Haliasos EC et al, Pediatr Dermatol 2013 SPITZOID LESIONS Spitz nevus  One of the most problematic topics in Dermatology and Dermatopathology  The best example of how dermoscopy has improved our diagnostic skills  The clinical recognition of Spitz nevus has improved from less than 50% to as much as 96%, especially for its pigmented variant (Steiner A et al, 1992) Classification of Spitzoid lesions

TWO CATEGORIES: BENIGN (NEVUS) OR MALIGNANT (MELANOMA)

OR

MORPHOBIOLOGIC SPECTRUM FROM BENIGNITY TO FULL- BLOWN MALIGNANCY Classification of Spitzoid lesions

SPITZ NEVUS SPITZOID MELANOMA

ATYPICAL SPITZOID SPITZ NEVUS SPITZOID NEVUS/TUMOR MELANOMA

ATYPICAL ATYPICAL SPITZOID SPITZ NEVUS SPITZOID SPITZOID MELANOMA NEVUS TUMOR

1. Mones JM, Ackerman AB, 2004, 2. Barnhill RL et al, 1999 3. Barnhill RL 2006 4. Da Forno PD et al, 2008 SPITZ NEVUS Epidemiology  <1% of childhood melanocytic nevi  Mostly whites  Both sexes almost equally affected or slight female predominance  Children, adolescents and young adults: 50%: <10 years 70%: <20 years  Favourable prognosis, but - increased risk for melanoma - moderate risk for regional lymph node metastasis Genetics  HRAS mutations in 11.8% of Spitz nevi  BRAF and NRAS mutations very rare Clinico-pathologic classification  Mainly a histopathological diagnosis  Two clinical variants: - Classic (non-pigmented) Spitz Nevus (rare) - Pigmented Spitz nevus or Reed Nevus (most common) Requena C et al, 2009; Ferrara G et al, 2005 Clinical presentation  Spitz nevi: small, well-circumscribed, pink-red or slightly pigmented, dome-shaped, smooth papules, or larger, sometimes variegated plaques  Pigmented Spitz nevi (Reed): symmetric, small, dark- brown to black macules or papules, or sometimes larger plaques  Predilection for face, neck, limbs and buttocks  Appear early in life  Rapid growth that calls the attention  Differential diagnosis: other melanocytic nevi, pyogenic granuloma, hemangioma, juvenile xanthogranuloma, and amelanotic melanoma Spitz nevi Dermoscopy of classic (non pigmented) Spitz nevus  Symmetric lesion  Sharply demarcated  Global pattern: - non-specific - homogeneous  Local features: - dotted vessels in regular distribution (~80%) - reticular depigmentation (white or inverse network) Dermoscopy of classic Spitz nevus

Dotted vessels

Reticular depigmentation

Courtesy of Dr Vincenzo Piccolo, Naples, Italy Dermoscopy of classic Spitz nevus

Dotted vessels Dermoscopy of pigmented Spitz nevus (Reed)  Heavily pigmented lesion  1-2 colors (blue-gray, dark brown, black)  Usually symmetric  Global pattern: - starburst (~50%) - globular (~25%) - multi-component (~25%)  Local features: peripheral streaks, regular globules, regular black network  Additional features: blue-white structures (blue-white veil or negative pigment network) Starburst paterrn

 Central area of homogenous blue to black pigmentation and peripheral, radially, and symmetrically distributed dark- brown to black streaks or pseudopods Starburst pattern Starburst pattern

Courtesy of Dr Vincenzo Piccolo, Naples, Italy Starburst pattern Starburst pattern Globular pattern

 Large brown to black globules regularly distributed, mostly at the periphery (Ferrara G et al, 2005) In contrast to globular/cobblestone nevi, pigmented SN show globules much more irregular in size and color and less densely distributed, as well as presence of black globules! Globular pattern Globular pattern + inverse network + dots

Globules Inverse network Globular pattern + inverse network + dots Multicomponent pattern Atypical  Combination of features network in an irregular fashion (Argenziano G et al, Eccentric Blue-white veil 1999) blotch  Asymmetry and multiple Streaks colors  Features: streaks, dots, globules, black network, blue-gray pigmentation, blue –white veil

Ferrara G et al, 2013 Differentiation from AST and SM is impossible by dermoscopy! ATYPICAL SPITZOID NEVUS/TUMOR Atypical spitzoid tumors  An unequivocal clinico-pathologic definition of AST is lacking  Atypical Spitzoid tumors (AST): melanocytic proliferations with intermediate histopathologic features between Spitz nevi (SN) and spitzoid melanoma (SM), carrying uncertain malignant potential Barnhill RL et al, 1999 Atypical Spitzoid tumor vs. Spitz nevus: Clinical characteristics  Size: - AST: medium to large - SN: small  Elevation: - AST: nodule (58.2%) or papule - SN: macule (42.7%) or plaque (38.2%)  Pigmentation - AST: up to half partly pigmented (52.7%), majority pink- red - SN: majority pigmented (brown-black) (70.9%)

Moscarela E et al, 2015 Atypical Spitzoid tumor vs. Spitz nevus: Dermoscopic characteristics  Global pattern: - AST: multicomponent (43.6%) > non-specific (20.0%) > non-pigmented typical spitzoid (16.4%) > typical pigmented spitzoid (3.6%) - SN: typical pigmented spitzoid (36.3%) > multicomponent (26.4%) > non-pigmented typical spitzoid (16.4%)  Vessels: - AST: linear irregular, short hairpin, glomerular, polymorphous - SN: dotted vessels in regular distribution

Moscarela E et al, 2015 Atypical spitzoid tumor (amelanotic): polymorhous vessels and inverse network

Polymorphous vessels

Zalaudek I, Master of Dermoscopy and Preventive Dermato- 2011 Atypical spitzoid tumor: non specific pattern

Pigment network

Linear irregular White lines vessels

Zalaudek I, Master of Dermoscopy and Preventive Dermato-oncology 2011 Atypical spitzoid tumor (hypomelanotic): multicomponent pattern

Courtesy of Dr Vincenzo Piccolo, Naples, Italy Atypical spitzoid nevus (pigmented)

Courtesy of Dr Vincenzo Piccolo, Naples, Italy Atypical spitzoid tumor (pigmented)

Moscarela E et al, 2015 SPITZOID MELANOMA Clinical characteristics

 Nodule or tumor  Non-pigmented > hypopigmented > pigmented Dermoscopic characteristics Asymmetry  Multiple colors  Global pattern: - non specific - multicomponent - starburst (irregular)  Local features: - asymmetrically distributed peripheral streaks, pseudopods, or globules - dotted vessels and inverse network or polymorphous vessels Sometimes tumors with symmetric, typical (non pigmented) spitzoid pattern, may turn out to be melanomas!

Moscarela E et al, 2015 Spitzoid melanoma: irregular starburst pattern Spitzoid melanoma: multicomponent pattern

Ferrara G et al, 2013 Spitzoid melanoma vs. Spitz nevus  SM: - Nodule or tumor - Non-pigmented with atypical or typical spitzoid pattern - Pigmented with multicomponent or irregular starburst pattern - Asymmetry Moscarela E et al, 2015  SN: - Macule or papule (flat) - Pigmented or non pigmented - Symmetry Only the typical starburst pattern is highly characteristic for benignity (96% diagnostic sensitivity) (Nino M et al, 2009) Likelihood of a spitzoid lesion to be a melanoma  The likelihood of finding melanoma when excising a completely symmetric spitzoid-looking lesion in patients aged 12 years or older is 13.3%  The risk significantly increases with increasing age, becoming 50% or higher after the age of 50 years Lallas A et al, 2015 Lallas A et al, 2014 Management of spitzoid lesions  Given - the rapid growth - the possibility to be a melanoma - the problem of accurately interpreting a spitzoid lesion Some clinicians are prone to remove all of spitzoid lesions (surgical excision with wide margins)  The possibility of a perfectly symmetric spitzoid-looking lesion to be a melanoma significantly increases with age Other follow a more conservative approach (follow up every 3-6 months), especially in children <12 years Broganelli P et al, 2014, Lallas A et al, 2015 Reasons to excise a spitzoid lesion  Age ≥ 12 years  Nodular lesion  Large lesion (>1cm)  Ulceration  Asymmetry  Amelanotic or hypopigmented lesion  Atypical dermoscopic features  Multicomponent or non specific pattern PEDIATRIC MELANOMA Epidemiology  Pediatric melanoma is extremely rare, especially before puberty (Lange JR, Balch SM, 2005)  1-4% o all MM arise in patients <20 years – only 0.3% before puberty  Less than 3% of all malignancies in childhood  Melanomas during adolescence (15-19 years old) are 10 times more frequent  Overall age-adjusted mortality rate for pediatric MM (USA): 2.25 deaths per year  Mortality rate strongly associated with age: 8-18 times higher after puberty (Lewis KJ, 2007) Campbell LB et al, 2015; Han D et al, 2012 Risk factors  Risk factors in children are similar as in adults  The importance of family history has been documented in children of all ages  Phenotypic and environmental factors (numerous acquired MN, history of and environmental factors are more important in older children  Genetic factors are more significant in younger children (Cordoro KM et al, 2013)  Most important risk factors: genetic conditions (xeroderma pigmentosum), immunosuppression, presence of large CMN (Tannous ZS et al, 2005) Histology  Pediatric melanomas are classified into: - Spitzoid melanoma (SM) - Non spitzoid melanoma (N-SM)

 SMM: younger age, nodular type with vertical growth phase, high Breslow thickness and mitotic rate, positive SLNB, more advanced stage  N-SMM: more often associated with a nevus, higher mortality rate Paradela S et al, 2012  Demographics , clinical and dermoscopic features are associated with the histopathologic subcategorization Carrera C et al, 2017 Genetics  Non spitzoid MM: - somatic single-nucleotide variations mainly affecting telomerase reverse transcriptase gene (TERT) promoter and activating BRAF mutations (Rabbie R et al, 2017)  Spitzoid MM: - chromosomal rearrangements, resulting in activated kinase signaling (Lu C et al, 2015) - does not harbor BRAF and NRAS mutation, thus genetically resembling Spitz nevus (Da Forno PD et al, 2008) Pediatric melanoma SPITZOID MELANOMA NON SPITZOID MELANOMA  More common in  Younger children (before adolescents puberty)  Risk factors present (fair  No asssociated risk factors skin, family history)  Amelanotic nodule arising  Pigmented lesion with MM suggestive features (SSM- de novo like)  Most commonly on the  Exhibite the classic ABCDE extremities and head criteria  Fulfill the modified ABCD  Most often on the back criteria  Commonly associated with a nevus (especially CMN)  Usually invasive, thick and  Increased risk for second ulcerated tumor primary MM (25% risk in 20 years) (Stanelle EJ et al, Carrera C et al, 2017 2015) Diagnosis  Diagnosis is challenging  Often considerable delay→ thicker tumors → worse prognosis (Carrera C et al, 2017)  Conventional ABCDE criteria are often not useful (Moscarela E et al, 2013)  Often, amelanotic papular/nodular lesion  Modified ABCD rule: Amelanotic, Bleeding bump, Color uniformity, De novo development of variable Diameter, (Cordoro KM et al, 2013)  Mimics: - other melanocytic lesion (non pigmented Spitz nevus) - non melanocytic lesions (pyogenic granuloma, viral wart, moluscum, angioma) (Mones JM, Ackerman AB, 2003) Differences between pediatric and adult melanoma

 Clinical presentation (amelanotic, nodular)  Higher Breslow thickness at presentation  Higher lymph node involvement  Overall better prognosis - lower potential for distant metastases - misdiagnosis ? (Leman JA et al, 2005) Ferrari A et al, 2005, Moore-Olufemi S et al, 2011 The Number Needed to Excise (NNE) for the pediatric population is 20 times higher than the rate in adults: 594 lesions excised to detect one melanoma!

Moscarella E et al, 2012 Dermoscopic diagnosis  Needs high level of suspicion  Pediatric melanoma often simulates common benign lesions (pyogenic granuloma, dermal nevi, common warts)

 Lesions with atypical dermoscopic characteristics  Lesions that can not be diagnosed with confidence as benign lesions by dermoscopy

EXCISION AND HISTOLOGIC EXAMINATION Dermoscopy of non spitzoid melanoma  The global pattern may be multicomponent or less often nevus-like pattern  The multicomponent pattern presents as in superficial spreading melanoma with at least 1 melanoma-specific dermoscopic feature present  Local features: atypical network (70%), irregular globules (50%), negative network (30%), blue white veil, atypical vessels.  The nevus-like pattern occurs in adolescence, is associated with family history of melanoma, and corresponds to melanomas caught at an earlier stage Carrera C et al, 2017 Non spitzoid melanomas in adolescents: multicomponent pattern

Carrera C et al, 2017 Non spitzoid melanomas in adolescents: nevus-like pattern

Carrera C et al, 2017 Dermoscopy of spitzoid melanoma (non pigmented)  The dermoscopic pattern is similar to the non pigmented Spitz nevus/tumor pattern  Local features: presence of atypical vessels (polymorphic vessels, dotted vessels), milky red areas, shiny white structures  The presence of both red color and shiny white structures increases the likelihood of the lesion being a spitzoid melanoma Carrera C et al, 2017 Dermoscopy of spitzoid melanoma (pigmented)  The dermoscopic pattern is similar to the pigmented Spitz nevus/tumor pattern (irregular starburst or multicomponent pattern)  Asymmetry + multiple colors (black, blue-gray, and dark brown)  Local features: peripheral streaks, irregular globules, dark blotches Carrera C et al, 2017 Spitzoid melanoma in children

Carrera C et al, 2017 Management  Early detection is the mainstay for favorable prognosis  Staging according to AJCC system  For suspect lesion: - narrow margin excision - evaluation by expert dermatopathologist  The role of SLNB is questionable (higher rate of sentinel lymph node involvement – less aggressive behavior)  When diagnosis confirmed: excision with sufficient wide margins  The role of adjuvant therapy is still under consideration  Regular follow-up according to protocols Moscarella E et al, 2013 Conclusions  «Suspicious moles» are a common reason for pediatric dermatologic consultation  Dermoscopy is the best tool available for the examination of melanocytic nevi in children  The majority of the lesions are benign and dermoscopy leads to the diagnosis with confidence, avoiding uneccessary excisions  Special attention should be given to melanocytic lesions with malignant potential (large CMN, cellular blue nevus, dysplastic nevi, Spitz nevus) that should be excised or followed systematically  Pediatric melanoma is rare and difficult to diagnose, because often mimics common benign lesions, but dermoscopy can better distinguish atypical lesions that should be excised and examined HELLAS/GREECE

Thank you for your attention!`