10.5826/dpc.1301a10
Introduction: A peripheral rim of globules represents a marker of horizontal growth phase in nevi and is a common feature in  children and adolescents. The observation of melanocytic lesion with peripheral globules (MLPG) in adulthood deserve more attention, since a melanoma may exhibits this feature albeit rarely. Risk stratified management recommendations considering a global clinical approach are still missing.
Objectives: To analyze current knowledge on MLPG and propose an integrated management algorithm stratified for age groups.
Methods: We conducted a narrative review of current published data on MPLG, analyzing clinical dermoscopic and confocal distinguishing features of melanoma from bening nevi.
Results: The risk of finding a melanoma when removing a MLPG increases with age especially in people &gt;55 years old and results significantly higher on extremities, head/neck and in case of a single asymmetrical lesion, ≥6 mm in diameter. Dermoscopic features associated to melanoma diagnosis include atypical peripheral globules, asymmetrical distribution,  multiple rims as well as globules reappearance after previous loss. In addition, wide blue-grey regression areas, atypical network, eccentric blotches, tan structureless peripheral areas and vascularizationare atypical dermoscopic features. Confocal worrisome findingss are represented by pagetoid cells within the epidermis, architectural disarrangement and atypical cells of the dermo-epidermal junction with irregular peripheral nests.
Conclusion: We proposed a multi-step age-stratified management algorithm integrating clinical, dermoscopic and confocal findings that may increase the early recognition of melanoma and avoid surgical excision of benign nevi.
text/xml
2160-9381
2360
en
Alessandro Di Stefani
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
dermoscopy
Melanocytic Lesions With Peripheral Globules: Proposal Of An Integrated Management Algorithm
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Review
2023-01-31
2022-02-05
2023-01-31
2023-02-27
e2023010
Dermatol Pract Concept
Introduction: A peripheral rim of globules represents a marker of horizontal growth phase in nevi and is a common feature in  children and adolescents. The observation of melanocytic lesion with peripheral globules (MLPG) in adulthood deserve more attention, since a melanoma may exhibits this feature albeit rarely. Risk stratified management recommendations considering a global clinical approach are still missing.
Objectives: To analyze current knowledge on MLPG and propose an integrated management algorithm stratified for age groups.
Methods: We conducted a narrative review of current published data on MPLG, analyzing clinical dermoscopic and confocal distinguishing features of melanoma from bening nevi.
Results: The risk of finding a melanoma when removing a MLPG increases with age especially in people &gt;55 years old and results significantly higher on extremities, head/neck and in case of a single asymmetrical lesion, ≥6 mm in diameter. Dermoscopic features associated to melanoma diagnosis include atypical peripheral globules, asymmetrical distribution,  multiple rims as well as globules reappearance after previous loss. In addition, wide blue-grey regression areas, atypical network, eccentric blotches, tan structureless peripheral areas and vascularizationare atypical dermoscopic features. Confocal worrisome findingss are represented by pagetoid cells within the epidermis, architectural disarrangement and atypical cells of the dermo-epidermal junction with irregular peripheral nests.
Conclusion: We proposed a multi-step age-stratified management algorithm integrating clinical, dermoscopic and confocal findings that may increase the early recognition of melanoma and avoid surgical excision of benign nevi.
Alessandro Di Stefani
2023/01/31
10.5826/dpc.1301a10
e2023010
UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy  2 Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy 
2160-9381
dermoscopy
en
e2023010
Lazaridou E, Fotiadou C, Apalla Z. Melanocytic lesions with peripheral globules: still a pitfall in the differential diagnosis of melanoma. J Eur Acad Dermatol Venereol. 2021;35(5):1040. DOI: 10.1111/jdv.17239. PMID: 33885195
Melanocytic Lesions With Peripheral Globules: Proposal Of An Integrated Management Algorithm
https://dpcj.org/index.php/dpc/article/download/2360/1950
    Melanocytic Lesions with Peripheral Globules:
  Proposal of an Integrated Management Algorithm
          Simone Cappilli1,2, Simone Ribero3, Luigi Cornacchia1,2, Silvia Catapano1,2,
       Laura Del Regno1, Laura Quattrini1,2, Alessandra D’Amore1,2, Francesco Federico4,
                   Paolo Broganelli3, Ketty Peris1,2, Alessandro Di Stefani1,2


1 UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli - IRCCS,
  Rome, Italy
2 Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
3 Dermatology Clinic, Department of Medical Sciences, University of Turin, Turin, Italy
4 Patologia, Dipartimento di Scienze della Vita e Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy



Key words: melanoma, reflectance confocal microscopy, diagnostic imaging, dermoscopy
Citation: Cappilli S, Ribero S, Cornacchia L, et al. Melanocytic Lesions With Peripheral Globules: Proposal Of An Integrated Management
Algorithm. Dermatol Pract Concept. 2023;13(1):e2023010. DOI: https://doi.org/10.5826/dpc.1301a10
Accepted: May 18, 2022; Published: January 2023
Copyright: ©2023 Cappilli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Simone Cappilli, MD, Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del
Sacro Cuore, Rome, Italy. Largo A. Gemelli 8, 00168, Rome, Italy. Tel.: +39 06-30154227 Fax: +39 06-30154919 Email: simo.cappilli@
gmail.com




  ABSTRACT             Introduction: A peripheral rim of globules represents a marker of the horizontal growth phase in
                       nevi and is a common feature in children and adolescents. The observation of melanocytic lesions
                       with peripheral globules (MLPGs) in adulthood deserves more attention, since melanoma may exhibit
                       this feature, albeit rarely. Risk-stratified management recommendations considering a global clinical
                       approach are still missing.
                       Objectives: To analyze current knowledge on MLPGs and propose an integrated management
                       ­algorithm stratified for age groups.
                       Methods: We conducted a narrative review of current published data on MLPGs, analyzing clinical
                       dermoscopic and confocal distinguishing features of melanoma from benign nevi.
                       Results: The risk of finding a melanoma when removing an MLPG increases with age, especially in
                       people >55 years old, and is significantly higher in the extremities, head/neck and in case of a single
                       asymmetrical lesion, ≥6 mm in diameter. Dermoscopic features associated with melanoma diagnosis
                       include atypical peripheral globules, asymmetrical distribution, multiple rims as well as the reap-
                       pearance of globules after prior loss. In addition, wide blue-grey regression areas, atypical networks,




Review | Dermatol Pract Concept. 2023;13(1):e2023010                                                                                      1
                      e­ ccentric blotches, tan structureless peripheral areas and vascularization are atypical dermoscopic fea-
                       tures. Confocal worrisome findings are represented by pagetoid cells within the epidermis, architectur-
                       al disarrangement and atypical cells of the dermo-epidermal junction with irregular peripheral nests.
                      Conclusion: We proposed a multi-step age-stratified management algorithm integrating clinical,
                      ­dermoscopic and confocal findings that may increase the early recognition of melanoma and avoid
                       surgical excision of benign nevi.




Introduction                                                       Objectives
A dermoscopic subset of melanocytic lesions is character-          The main aim of this manuscript is to critically review the cur-
ized by the presence of round to oval globules regularly           rent published data on MLPGs and to provide an integrated
distributed at the edge of the lesion, representing a marker       clinical, dermoscopic and confocal management algorithm
of the horizontal enlargement with a mean growth rate of           stratified for age groups, resulting in a more ­appropriate and
         2
0.25mm /month [1,2]. A decreased density or a complete             individualized management strategy.
disappearance of peripheral globules has been associated
with a stabilization of nevi, with an estimated median time of
growth cessation of 58.6 months (4-5 years) [1,3]. Enlarge-        Methods
ment of nevi is commonly observed in children and adoles-
                                                                   Search Strategy
cents with a linear age-related prevalence reduction [3,4].
                                                                   To identify eligible studies, a comprehensive search was con-
The common approach towards melanocytic lesions with
                                                                   ducted using PubMed electronic database with the following
peripheral globules (MLPGs) in patients younger than
                                                                   terms: “dermoscopy (MeSH)”, “dermatoscopy (MeSH)”,
35 years is conservative, not requiring interventions, as
                                                                   “confocal    microscopy     (MeSH),    “melanocytic     lesions
regards their benign clinical behavior [2,3]. The occur-
                                                                   (MeSH)”, “melanoma (MeSH)” and any one of the terms
rence of MLPGs in adulthood and the elderly is infre-
                                                                   “peripheral clods (MeSH)”, “peripheral globules (MeSH)”
quent and requires a ­
                     cautious approach, since change
                                                                   published in English. The main search and the screening of
over time represents a suspicious feature [3]. Further-
                                                                   titles and abstracts were completed independently by two re-
more, peripheral globules may also be detected, albeit
                                                                   viewers (SC and LC). The manual search was concluded by
rarely, in melanoma [3,5]. In 2007, the International
                                                                   the perusal of the reference sections of all relevant articles.
Dermoscopic Society recommended that MLPGs exhib-
                                                                   All studies identified as relevant were analyzed and included.
iting asymmetry of structures within the lesion should
                                                                   Case reports aiming to describe singular observations or
be closely monitored or excised, regardless of age [6].
                                                                   written in non-native English language were excluded.
Afterwards, it has been suggested to monitor MLPGs in the
absence of other dermoscopic m
                             ­ elanoma-specific criteria
beyond the age of 30, considering instead surgical excision        Results
or close follow-up for those over 50 [3].
    Reflectance confocal microscopy (RCM) allowed the
                                                                   Search Results
accurate definition of globules as junctional clusters of me-      We completed a literature review by searching the electronic
lanocytes protruding into dermal papillae, or widening the         database PubMed until 1 December 2021, for all relevant
interpapillary space, at the edge of the lesions with a perfect    records. A total of 125 articles were retrieved in the data syn-
correspondence to histology [7]. Consecutive confocal evalu-       thesis: 120 were excluded due to being duplicated (among
ations of MLPGs in adults supported the dynamic evolution          MeSH terms), not written in English, and not relevant (not
of this process, through an eccentric elongation of junctional     related to melanocytic lesions). Finally, a total number of 5
clusters with narrowing of their shape, associated with a cen-     studies were included and analyzed, and their main features
trifugal extension [7].                                            are summarized in Table 1.
    Recent studies have been focused on the clinical ap-
proach to MLPGs, providing further insights into MLPGs,            Age and Clinical Data
however heterogeneous management strategies have been              The impact of patient age on clinical decision-making for
proposed and common practical indications are still missing        MLPGs is well acknowledged but different thresholds and
[5, 8-12].                                                         suggestions have been proposed [5,8-11]. Williams et al



2                                                                              Review | Dermatol Pract Concept. 2023;13(1):e2023010
                  Table 1. Included studies on melanocytic lesions with peripheral globules.
             Study                              Study design                           Participant’s age            No. of cases
 Williams et al. 2020              Retrospective study                        >20 yo                               95 nevi
                                                                                                                   4 MM
 Ribero et al. 2020                Retrospective study                        35-85 yo                             412 nevi
                                                                              (median age 49)                      45 MM
                                                                                                                   - 19 in situ
                                                                                                                   - 26 invasive
 Reiter et al. 2021                Cross-sectional, retrospective study       2- 85 yo                             178 nevi
                                                                              (median age of MM=50 yo,             115 MM
                                                                              median age of nevi=34 yo )
 Pampín-Franco et al. 2021         Prospective study, high risk patients      19-73 yo                             151 nevi
                                                                              (median age 42 yo)                   3 MM
                                                                                                                   - 3 invasive
 Carbone et al. 2021               Prospective study, high-risk patients      16-79 yo                             116 nevi
                                                                              (median age 41 yo)                   19 MM
                                                                                                                   - 5 in situ
                                                                                                                   - 14 invasive

MM= malignant melanoma, yo= years old




observed all confirmed cases of melanoma (4/99, 4.0% of             [5, 8-11]. In addition, Pampìn-Francoin et al. reported an av-
MLPGs) in adulthood, specifically in individuals aged 30,           erage size of MLPGs of 4.1 mm with a significant association
35, 40 and 55, without difference in the proportion of ma-          with the diagnosis of melanoma in lesions ≥6mm in diameter,
lignancy, when dichotomizing by age 50 (5.3% vs 3.9%,               as well as in MLPGs showing asymmetry in two axes [10].
p=1.0) [11]. Conversely, Ribero et al observed 9.8% of              Moreover, the authors highlighted that multiple MLPGs in a
MLPGs (45/457) being melanomas (age ranged from 35 to               single patient were statistically less likely to be diagnosed as
85 years) with a dramatic increase of frequency in patients         melanoma [10] (Table 2).
>55 years old (10/69, 15%) [5]. Two other studies found a
positive trend between histologically proven dysplastic nevi        Dermoscopy
and melanoma with patients’ ages, even though without               The morphology and distribution of peripheral globules along
statistical significance [9,10]. In particular, Reiter et al. re-   with the presence of additional atypical features in MLPGs
ported a diagnosis of melanoma for 39.2% (115/293) of to-           was recently investigated, with the objective to identify spe-
tal MLPGs with an average age of 50 years old (range 20-85          cific structures indicating a diagnosis of melanoma [8-11].
years old), and more than half of cases (68%) being younger            Dermoscopic findings that support a diagnosis of mela-
than 60 years old [9]. A lower percentage of melanoma               noma included atypical globules (irregular in shape, size or
(1.9%, 3/154 MLPGs) was observed by Pampín-­Francoin                color) and/or their asymmetrical distribution. Completely
et al with 49.5 years old estimated as the median age of            circumferential atypical globules are reported to have the
malignancy in high-risk patients, defined as patients under         highest risk of being melanoma, followed by focal circum-
digital dermoscopic surveillance for atypical mole syndrome         ferential atypical globules and focal circumferential typical
and/or personal or familial history of melanoma [10]. In a          globules [9]. Globules distributed in more than a single rim
similar selected population of high-risk adults, Carbone et al      (tiered) and departing within the edge of a lesion were found
reported a higher rate of malignancy with 19 melanomas in           to be more frequently observed in melanoma rather than
135 MLPGs (14%) with a mean age of 49.8 years old and               nevi, as were peripheral globules covering less than 25%
10% of cases occurring even in patients under 30 years old          of the entire circumference (especially in case of <1-history)
[8] (Table 1).                                                      [9,10]. In addition, the reappearance of peripheral globules
   Concerning the anatomic site of MLPGs, the most com-             after their previous disappearance has been also related to a
mon location was the torso and especially the back [5,8-10],        diagnosis of melanoma, and this finding is in contrast with
while the risk of finding a melanoma when removing an               the expected evolution of MLPGs [2,10].
MLPG resulted significantly higher in the extremities and              Other relevant diagnostic clues suggesting melanoma
head/neck [5,9]. A gender prevalence of MPLGs was largely           were the presence of blue-grey regression areas (especially
not reported except for two studies with controversial results      when involving a large part of an MLPG, >50%) and atypical



Review | Dermatol Pract Concept. 2023;13(1):e2023010                                                                               3
    Table 2. Clinical, dermoscopic and confocal criteria associated with the diagnosis of melanoma
                                     showing peripheral globules.
             Clinical Data                                  Dermoscopy                                             RCM
 Extremities and head/neck          Regular PG with at least 2 melanoma-specific structures          Epidermis
 Single lesion rather than          OR                                                               Pagetoid cells (roundish or
 multiple MLPG                      ≥2 of the following findings                                     dendritic)
 ≥6 mm diameter                     PG in less than 25% of the circumference with                    DEJ
 Asymmetry in two axes              1 year history                                                   Unspecific pattern
                                    Reappearance of PG                                               Non-edged dermal papillae
                                    PG irregular in size, shape, or color                            Architectural disarrangement
                                    Atypical and/or asymmetric distribution of PG                    Atypical thickenings
                                    Blue-grey regression structures involving >50%                   Atypical cells
                                    of the lesion                                                    Peripheral dense irregular
                                    Vascularization                                                  (sparse) nests
                                    Off-center blotches
                                    Peripheral tan structureless areas

rcm= reflectance confocal microscopy, mlpg= melanocytic lesions with peripheral globules, pg= peripheral globules, dej= dermal-epidermal
junction


networks [10]. Eccentric blotches, tan structureless periph-          papillary dermis were seen either in benign nevi or in mel-
eral areas and vascularization were also considered worri-            anomas [10].
some features [10,11]. In presence of a regular distribution
of peripheral globules, at least two melanoma-­specific crite-        Proposal of an Integrated Management Algorithm
ria were considered indicative of malignancy by Reiter et al,         Herein we propose a flowchart algorithm for individualized
while for Williams et al a single melanoma s­ pecific-structure       management of MLPGs considering clinical, dermoscopic
was sufficient, although such circumstance was observed               and confocal criteria, with the aim to identify melanomas at
in more than half of nevi and in all melanoma cases (Table            an early stage and to reduce as much as possible the unnec-
2) [9,11].                                                            essary surgical excision of benign nevi (Figure 1). The pro-
    Remarkably, the risk of an MLPG being a melanoma                  posed algorithm is outlined to provide risk stratification and
remains not negligible even for lesions that exhibit only             includes the following steps:
peripheral regular globules without additional worrisome
­                                                                         MLPGs in Patients <35 Years Old: regular dermoscopic
dermoscopic criteria [5].                                             monitoring is recommended for lesions showing an orga-
                                                                      nized rim of globules with a reticular, globular, or mixed
Confocal Microscopy                                                   central pattern. A decreased density of peripheral globules
In-vivo confocal evaluation of MLPGs, with a detailed anal-           resulting in total disappearance, in an overall period of 4-5
ysis of global architecture and cytological aspects, was per-         years, is expected. This clinical evolution allows the inter-
formed in two studies [8,10]. Classical melanoma-specific             ruption of follow-up surveillance at the end of the process.
findings were detected in 100% of malignant MLPGs                     We suggest performing RCM in MLPGs when at least two
[8,10]. In detail, the presence of intraepidermal pagetoid            atypical dermoscopic structures are detected, as we still con-
cells (roundish or dendritic in shape) was strongly related           sider the very low percentage of melanoma exhibiting this
to the diagnosis of melanoma [10]. Moreover, architectural            pattern in patients younger than 35 years old. In the absence
disarray of the dermo-epidermal junction (DEJ), unspecific            of cyto-architectural atypia a dermoscopic follow-up can be
pattern or non-edged dermal papillae, and atypical junction           extended whereas in presence of confocal m
                                                                                                               ­ elanoma-specific
thickening represented confocal findings more frequently              criteria, surgical excision is recommended (­ Figure 2). MLPGs
observed in malignant lesions. Atypical cells at the DEJ, es-         showing ≥2 new-onset atypical dermoscopic structures during
pecially when multiple, along with the presence of irregu-            dermoscopic surveillance should be further investigated by
lar and sparse peripheral nests with an evident cleft, were           means of RCM and follow the same recommendations.
also reported as being associated with histologically proven              MLPGs in Patients 35-55 Years Old: In this age group,
melanomas (Table 2) [8,10]. No lesions showed true cere-              MLPGs should be managed with more caution, with a
briform nets. Inflammatory cells and melanophages at the              careful assessment of dermoscopic features: if any atypical



4                                                                                 Review | Dermatol Pract Concept. 2023;13(1):e2023010
                          <35 YO                                                       35–55 yo                               >55 yo




                                                                                     DERMOSCOPY             YES
                        DERMOSCOPY
                                                                                       ATYPICAL                   EXCISION
                    ATYPICAL STRUCTURES
                                                                                     STRUCTURES


                               ≥2         EXCISION                                             NO


                                           YES
DERMOSCOPY                  RCM                      <2   DERMOSCOPY                     RCM
                                                                                                            YES              EXCISION
ONSET OF NEW            MELANOMA                          ONSET OF NEW               MELANOMA
  CRITERIA            SPECIFIC CRITERIA                     CRITERIA               SPECIFIC CRITERIA



                                   NO
                                                                                             NO

                    REQULAR FOLLOW-UP
                    UNTIL STABILIZATION                                           REQULAR FOLLOW-UP
                                                                                  UNTIL STABILIZATION


Figure 1. Our proposed algorithm for the clinical management of melanocytic lesions with peripheral globules, including dermoscopic and
confocal findings in different age groups.




                 Figure 2. Invasive melanoma (Breslow 0.9 mm) on the upper back of a 33-years old man: dermoscopy
                 (a), RCM (b,c) and histology (d). Irregular blotches, shiny white streaks and blue-whitish veils are ob-
                 served at dermoscopy beyond a regular distribution of peripheral globules (a). A confocal section of the
                 dermal-epidermal junction displays dendritic cells and sparse nests (blue squares) (b, low magnification;
                 c, high magnification) corresponding to the epidermal spreading of melanocytes and discohesive nests
                 seen on histology (d) [Haematoxylin and eosin stain, original magnification x200].




Review | Dermatol Pract Concept. 2023;13(1):e2023010                                                                                    5
                Figure 3. Nevus on the right leg of a 46-year-old woman: dermoscopy (a), RCM (b,c) and histology (d).
                Peripheral globules are symmetrically organized at the edge of the lesion (a), corresponding to dense
                melanocytic nests (blue squares) located at the dermal-epidermal junction and papillary dermis upon
                confocal view at low (b) and high (c) magnification. A ringed pattern composed of edged dermal papillae
                is observed in the central area (b). Junctional melanocytic nests are observed at histopathology (d) [Hae-
                matoxylin and eosin stain, original magnification x200].




dermoscopic structure is detected, surgical excision is rec-           warning signal and the chance of an MLPG being a mela-
ommended. In addition, we suggest performing RCM evalu-                noma exhibiting only organized peripheral globules without
ation also in the absence of melanoma-specific dermoscopic             other worrisome dermoscopic features represents a concrete
criteria (Figure 3). Confocal cyto-architectural irregular fea-        risk after 55 years old [5].
tures require surgical excision of the lesion, while a regular
follow-up is suggested in case of reassuring findings. During          Limitations
the follow-up period, surgery is recommended where new                 A limitation of this work is the inclusion of different stud-
atypical dermoscopic criteria are observed.                            ies with heterogeneous methodological cohorts and inter-
    The decision to perform RCM in the range of 35-55                  ventions, with no age-group standardisation. In addition,
years old, even in presence of reassuring dermoscopic crite-           it should be considered that non-proven histologic MLPGs
ria, is due to the still not negligible risk of a regular MLPG         were not considered in the studies, and this may have con-
being a melanoma. Indeed, 50 years old was assessed as the             tributed to a realistic underestimation of benign nevi exhib-
median age of patients with a proven histological diagnosis            iting peripheral globules. This scenario may be due to the
of melanoma in different studies [9,10] and confocal eval-             most common approach of favoring a surveillance program
uation has been demonstrated to disclose irregular/atypi-              of MLPGs over time, under 35 years old in daily practice.
cal findings with a 100% sensitivity for the diagnosis of              Lastly, data synthesising dermoscopic and confocal criteria
MM [8,10].                                                             were retrieved from a small number of studies, and larger
    MLPGs in Patients >55 Years Old: in this age group, the            prospective datasets are needed to validate the utility of the
suggested management is surgical excision in all cases. While          proposed algorithm. The suggested management indications
growth markers of melanocytic lesions are expected in young            should be interpreted with caution and individualized for ev-
adults, the observation of MLPGs in the elderly represents a           ery single patient.


6                                                                                  Review | Dermatol Pract Concept. 2023;13(1):e2023010
Conclusions                                                               6. Bowling J, Argenziano G, Azenha A. et al. Dermoscopy key
                                                                             points: recommendations from the international dermoscopy so-
MLPGs are frequently seen in daily practice and represent                    ciety. Dermatology. 2007;214(1):3-5. DOI: 10.1159/000096904.
                                                                             PMID: 17191039
a clinical challenge requiring the most appropriate manage-
                                                                          7. Pellacani G, Scope A, Ferrari B. et al. New insights into nevo-
ment for individual patients. Herein we propose a multi-step                 genesis: in vivo characterization and follow-up of melanocytic
and age-based management algorithm based on current pub-                     nevi by reflectance confocal microscopy. J Am Acad Dermatol.
lished data integrating clinical, dermoscopic and confocal                   2009 ;61(6):1001-13. DOI: 10.1016/j.jaad.2009.04.018. PMID:
findings, in order to increase the early recognition of mela-                19833408
noma and avoid surgical excision of benign lesions.                       8. Carbone A, Persechino F, Paolino G et al. Enlarging mela-
                                                                             nocytic lesions with peripheral globular pattern: a dermos-
                                                                             copy and confocal microscopy study. Ital J Dermatol Venerol.
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Review | Dermatol Pract Concept. 2023;13(1):e2023010                                                                                           7
