10.5826/dpc.1302a101
Introduction: Facial lentigo maligna/lentigo maligna melanoma (LM/LMM) is a significant diagnostic clinical challenge and dermoscopy can help its diagnosis.
Objectives: The following study aimed to evaluate if super-high magnification dermoscopy at 400x can add further details for the diagnosis of the LM/LMM.
Methods: This is a retrospective observational, multicentric study enrolling patients who received a 20x and 400x (D400) magnification dermoscopic examination of facial skin lesions in clinical differential diagnosis with LM/LMM. Dermoscopic images were retrospectively evaluated by four observers for the presence/absence of nine 20x and ten 400x dermoscopic features. Univariate and multivariate analyses were carried out to find predictors of LM/LMM.
Results: We enrolled 61 patients with a single atypical skin lesion of the face, including 23 LMs and 3 LMMs. The presence of roundish and/or dendritic melanocytes (P &lt; 0.001), irregular arrangement of melanocytes (P &lt;0.001), irregular in shape and size melanocytes (P = 0.002), and folliculotropism of melanocytes (P &lt;0.001) at D400 were more frequent in LM/LMM than other facial lesions. According to the multivariate analysis, roundish melanocytes at 400x dermoscopy were more indicative of LM/LMM (Odds Ratio-OR 49.25, 95% CI 8.75-513.2, P &lt; 0.001), and sharply demarcated borders at 20x dermoscopy were more indicative of not-LM/LMM (OR 0.1, 95% CI 0.01-0.79, P = 0.038).
Conclusions: D400 can identify atypical melanocyte proliferation and folliculotropism that can help to identify LM/LMM together with conventional dermoscopy data. Our preliminary observations should be confirmed by larger studies.
text/xml
2160-9381
2721
en
Jean Luc Perrot
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
melanoma
  Super-High Magnification Dermoscopy Can Help for the Diagnosis of Lentigo Maligna: a Pilot Study on 61 Cases
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-04-29
2022-07-28
2023-04-29
2023-05-31
e2023101
Dermatol Pract Concept
Introduction: Facial lentigo maligna/lentigo maligna melanoma (LM/LMM) is a significant diagnostic clinical challenge and dermoscopy can help its diagnosis.
Objectives: The following study aimed to evaluate if super-high magnification dermoscopy at 400x can add further details for the diagnosis of the LM/LMM.
Methods: This is a retrospective observational, multicentric study enrolling patients who received a 20x and 400x (D400) magnification dermoscopic examination of facial skin lesions in clinical differential diagnosis with LM/LMM. Dermoscopic images were retrospectively evaluated by four observers for the presence/absence of nine 20x and ten 400x dermoscopic features. Univariate and multivariate analyses were carried out to find predictors of LM/LMM.
Results: We enrolled 61 patients with a single atypical skin lesion of the face, including 23 LMs and 3 LMMs. The presence of roundish and/or dendritic melanocytes (P &lt; 0.001), irregular arrangement of melanocytes (P &lt;0.001), irregular in shape and size melanocytes (P = 0.002), and folliculotropism of melanocytes (P &lt;0.001) at D400 were more frequent in LM/LMM than other facial lesions. According to the multivariate analysis, roundish melanocytes at 400x dermoscopy were more indicative of LM/LMM (Odds Ratio-OR 49.25, 95% CI 8.75-513.2, P &lt; 0.001), and sharply demarcated borders at 20x dermoscopy were more indicative of not-LM/LMM (OR 0.1, 95% CI 0.01-0.79, P = 0.038).
Conclusions: D400 can identify atypical melanocyte proliferation and folliculotropism that can help to identify LM/LMM together with conventional dermoscopy data. Our preliminary observations should be confirmed by larger studies.
Jean Luc Perrot
2023/04/29
10.5826/dpc.1302a101
e2023101
Department of Dermatology, University Hospital of Saint-Etienne, Saint-Etienne, France
2160-9381
melanoma
en
e2023101
Akay BN, Kocyigit P, Heper AO, Erdem C. Dermatoscopy of flat pigmented facial lesions: diagnostic challenge between pigmented actinic keratosis and lentigo maligna. Br J Dermatol 2010; 163: 1212-7.
  Super-High Magnification Dermoscopy Can Help for the Diagnosis of Lentigo Maligna: a Pilot Study on 61 Cases
https://dpcj.org/index.php/dpc/article/download/2721/2065
  Super-High Magnification Dermoscopy Can Help
 for the Diagnosis of Lentigo Maligna: a Pilot Study
                    on 61 Cases
               Elisa Cinotti1, Alessandra Cartocci2, Flavio Giulio Liso1, Vittoria Cioppa1,
                Francesca Falcinelli1, Linda Tognetti1, Pietro Rubegni1, Jean Luc Perrot3


1 Department of Medical, Surgical and Neurological Science, Dermatology Section, University of Siena, S. Maria alle Scotte Hospital, Siena, Italy
2 Department of Medical Biotechnology, University of Siena, Siena, Italy
3 Department of Dermatology, University Hospital of Saint-Etienne, Saint-Etienne, France



Key words: dermoscopy, super-high magnification, melanocyte, lentigo maligna, melanoma
Citation: Cinotti E, Cartocci A, Liso FG, et al. Super-High Magnification Dermoscopy Can Help for the Diagnosis of Lentigo Maligna:
a Pilot Study on 61 Cases. Dermatol Pract Concept. 2023;13(2):e2023101. DOI: https://doi.org/10.5826/dpc.1302a101
Accepted: October 21, 2022; Published: April 2023
Copyright: ©2023 Cinotti 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: Vittoria Cioppa, Department of Medical, Surgical and Neurological Science - Dermatology Section,
University of Siena, S. Maria alle Scotte Hospital, Viale Bracci 16, 53100 Siena, Italy. Tel: 0039-0577 585428. Fax: 0039 0577 585488,
E-mail: v.cioppa@student.unisi.it




  ABSTRACT              Introduction: Facial lentigo maligna/lentigo maligna melanoma (LM/LMM) is a significant diagnos-
                        tic clinical challenge and dermoscopy can help its diagnosis.
                        Objectives: The following study aimed to evaluate if super-high magnification dermoscopy at 400x
                        can add further details for the diagnosis of the LM/LMM.
                        Methods: This is a retrospective observational, multicentric study enrolling patients who received a
                        20x and 400x (D400) magnification dermoscopic examination of facial skin lesions in clinical differ-
                        ential diagnosis with LM/LMM. Dermoscopic images were retrospectively evaluated by four observers
                        for the presence/absence of nine 20x and ten 400x dermoscopic features. Univariate and multivariate
                        analyses were carried out to find predictors of LM/LMM.
                        Results: We enrolled 61 patients with a single atypical skin lesion of the face, including 23 LMs and 3
                        LMMs. The presence of roundish and/or dendritic melanocytes (P < 0.001), irregular arrangement of
                        melanocytes (P <0.001), irregular in shape and size melanocytes (P = 0.002), and folliculotropism of
                        melanocytes (P <0.001) at D400 were more frequent in LM/LMM than other facial lesions. According
                        to the multivariate analysis, roundish melanocytes at 400x dermoscopy were more indicative of LM/
                        LMM (Odds Ratio-OR 49.25, 95% CI 8.75-513.2, P < 0.001), and sharply demarcated borders at 20x
                        dermoscopy were more indicative of not-LM/LMM (OR 0.1, 95% CI 0.01-0.79, P = 0.038).
                        Conclusions: D400 can identify atypical melanocyte proliferation and folliculotropism that can help
                        to identify LM/LMM together with conventional dermoscopy data. Our preliminary observations
                        should be confirmed by larger studies.


Original Article | Dermatol Pract Concept. 2023;13(2):e2023101                                                                                 1
Introduction                                                        or Saint-Etienne (France) for a dermatological examination
                                                                    between the 1st January 2018 and 31st December 2020. Data
Although cutaneous melanoma represents 4% of the overall            were analyzed from April 2021 to June 2021. The study was
tumor amount in the whole body, it is a public health is-           conducted according to the criteria set by the Declaration of
sue, particularly in fair-skinned populations, due to its high      Helsinki. All data were de-identified before use. All patients
morbidity and mortality [1,2-4]. The head and neck region           gave their consent to the processing of their data.
is of particular interest for melanoma; despite accounting
for only 9% of the total body surface, it harbors 20% of            Participants
melanoma cases, mainly of lentigo maligna/lentigo maligna           We enrolled non-consecutive patients with pigmented skin
melanoma (LM/LMM) subtype [5]. LM and LMM appear                    lesions of the face that needed to be removed or followed
on sun-damaged skin, most often on the head and neck and            up for their atypical clinical and/or 20x dermoscopic fea-
in elderly patients [6].                                            tures according to a skin imaging expert dermatologist
    Over the last three decades, the global incidence of mela-      (E.C. or J.L.P.).
noma has steadily increased, and the current increase in life ex-
pectancy of the population could also favor the development         Data Sources
of LM/LMM [7,8]. Despite recent advances in both diagnosis
                                                                    For this study, we selected only patients who received a 20x
and treatment, cutaneous melanoma continues to represent
                                                                    and 400x (D400) magnification dermoscopic examination
a significant clinical challenge [9]. Earlier detection of mela-
                                                                    of facial lesions in clinical differential diagnosis with LM/
noma improves the survival rates but the clinical presentation
                                                                    LMM. These lesions were recorded with the videodermo-
of LM/LMM can be subtle and varied [10]. The differential
                                                                    scope Fotofinder Medicam 1000 (Fotofinder System, Bad
diagnosis of LM/LMM includes pigmented actinic keratoses,
                                                                    Birnbach).
solar lentigines, seborrheic keratoses, and lichen planus-like
                                                                       To perform D400, we used the same camera as for 20x
keratoses [11]. Also, early LM may not exhibit the tell-tale
                                                                    video-dermoscopy and we changed the terminal lens. Spe-
signs of an evolving melanoma (changes in diameter, border,
                                                                    cialists in skin imaging (E.C. and J.L.P), acquired at least
color, and asymmetry), and it is often difficult to distinguish
                                                                    5 images for each lesion, for a total of 1138 images of 61
from the surrounding sun-damaged skin [12].
                                                                    skin lesions, as D400 does not show an entire lesion (D400
    Although histological evaluation, remains the gold
                                                                    field of view of 1 mm x 0.5625 mm). We included cases with
standard for the confirmation of the diagnosis, several
                                                                    histological diagnosis or lesions unmodified at clinical and
non-invasive imaging procedures such as dermoscopy and
                                                                    dermoscopic follow-up of at least 12 months.
reflectance confocal microscopy (RCM) may improve LM/
LMM clinical diagnostic accuracy [13-15]. Moreover, they
                                                                    Variables
can help in biopsy site selection, margin delineation, and
                                                                    For the clinical variables, we evaluated the patient sex and
treatment monitoring.
                                                                    age. A group of 4 dermatologists (E.C, F.G.L., F.F., and V.C.)
    Recently, our group has shown that dermoscopy at 400x
                                                                    belonging to the University Departure of Dermatology of the
magnification (D400 or super-high magnification dermos-
                                                                    Hospital-University of Siena evaluated the images and de-
copy) can aid the non-invasive diagnosis of melanoma by
                                                                    fined the dermoscopy variables to be analyzed.
observing single pigmented cells [16,17].
                                                                       The 20x dermoscopy variables included: benign bench-
                                                                    marks (white and wide follicular opening, reticular or par-
Objectives                                                          allel brown lines, sharply demarcated borders, mila-like
                                                                    cysts/comedo-like openings, erythema and red pseudo-net-
The following study aimed to evaluate if D400 can add fur-
                                                                    work) and malignant benchmarks (polygons/rhomboids/zig-
ther details for the clinical diagnosis of the LM/LMM and its
                                                                    zag pattern/angulated lines, annular granular pattern / gray
differential diagnosis with other facial lesions.
                                                                    circles, asymmetrical pigmented follicular openings, and fol-
                                                                    licular obliteration).
Methods                                                                The D400 variables were the presence of the pigmented
                                                                    cells and their features, out of focus blue or gray/brown
Study Design                                                        structureless areas, vessels, and their shape (linear/arbor-
Retrospective observational, multicentric study.                    izing, and irregular), hyperkeratotic roundish concentric
                                                                    structures, and folliculotropism of melanocytes. Pigmented
Setting                                                             cells were differentiated into keratinocytes (seen as polygo-
Data were collected on patients who came to the Dermatol-           nal brown regular mostly in focus cells, evenly spread and/
ogy department of the University Hospital of Siena (Italy)          or inside a network), roundish melanocytes (seen as large


2                                                                       Original Article | Dermatol Pract Concept. 2023;13(2):e2023101
roundish brown-to violet/blue scattered cells; cells were de-              with a single atypical skin lesion of the face, were selected.
fined as “large” when they were larger than keratinocytes),                The 61 skin lesions included 23 LMs, 3 LMMs, 15 solar len-
dendritic melanocytes (large dendritic brown-to-violet/blue                tigines, 12 seborrheic keratoses, 6 lichenoid keratoses, and 2
scattered cells), and melanophages (large blue-to-violet non               pigmented actinic keratoses.
in focus cells with a not defined polymorphous shape). Con-
sidered cell features were cell color (violet and blue colors              20x Dermoscopy
are difficult to differentiate with D400 and were considered               20x dermoscopy features are reported in Table 1. Con-
together; light and dark brown were also considered together               cerning malignant benchmarks, the annular-granular pat-
because brown is often present with multiple shades in the                 tern and gray circles were more frequent in LM/LMM
same structure), shape and size irregularity of melanocytes,               than in the other lesions [Figure1, 19 LM/LMMs (73.1%)
and irregular arrangement of single melanocytes.                           and 14(41.2%) P = 0.019]; asymmetric pigmented follicu-
                                                                           lar openings and follicular obliteration were not present
Statistical Analysis                                                       in any of the benign lesions analyzed, while these features
Descriptive statistics were performed: absolute frequencies                were associated to LM/LMMs (P < 0.001). Regarding be-
and percentages were calculated for qualitative variables and              nign benchmarks, sharply demarcated borders were present
mean and standard deviations for the quantitative ones. The                in 17 (50%) not-LM/LMM lesions and only three (11.5%)
association between qualitative variables and the outcome (ie              LM/LMMs (P = 0.002), while the presence of milia-like
LM/not LM) and 20x dermoscopy or D400 was evaluated                        cysts/comedo-like openings was detected in seven (20.6%)
by Fisher exact test. T-test was carried out if the variables              not-LM/LMM lesions and no LM/LMMs (P = 0.016).
were normally distributed (normal distribution evaluated
by Kolmogorov Smirnov test) and there was homoscedas-                      400x Dermoscopy
ticity between variances evaluated by Bartlett test, otherwise             400x dermoscopy features are reported in Table 2. The pres-
Mann-Whitney test was used. Logistic regression was later                  ence of roundish and/or dendritic melanocytes was mainly
performed to evaluate variables that were statistically sig-               observed in skin lesions diagnosed as LM/LMM compared
nificant at the previous univariate analysis (P < 0.05). The               to the other lesions (Figure 1, P < 0.001). Roundish melano-
best subset of variables was selected by a stepwise procedure              cytes were seen in four not-LM/LMM lesions (11.4%) and
based on Akaike criterion. Odds ratio (OR) and 95% con-                    24 LM/LMMs (92.3%), while dendritic melanocytes were
fidence intervals (CI) were estimated by logistic regression.              found in seven not LM/LMM lesions (20.0%) and 25 LM/
The analyses were carried out by R software version 3.6.2.                 LMMs (96.2%). Pigmented keratinocytes were present in al-
                                                                           most all the images analyzed (Figure 2). Besides, LM/LMM
Results                                                                    showed more frequently than the other facial lesions mela-
                                                                           nocytes with irregular arrangement (P < 0.001) and irregu-
Participants and Lesion Data                                               larity in shape and size (P = 0.002).
In this study 61 patients, 32 (52%) women and 29(48%)                          Cell color, out-of-focus bluish or gray/brown structure-
men, with a mean age of 72.3 years (range 44 – 91 years)                   less areas and vessel presence were not statistically significant


                                     Table 1. 20x dermoscopy features of facial lesions.
                                                                                 LM/LMM                  Othera
                                                                                   N=26                   N=35
                                                                                   n(%)                   n(%)                 P-value
    White and wide follicular opening                                             0 (0.0)                3 (8.8)                 0.251
    Reticular or parallel brown lines                                            10 (38.5)              8 (23.5)                 0.261
    Sharply demarcated borders                                                    3 (11.5)              17 (50.0)                0.002
    Milia like cysts /comedo-like openings                                        0 (0.0)               7 (20.6)                 0.016
    Erythema                                                                      4 (15.4)              4 (11.8)                 0.717
    Polygons / rhomboids / zig-zag pattern / angulated lines                      3 (11.5)              7 (20.6)                 0.491
    Annular granular pattern / Gray circles                                      19 (73.1)              14 (41.2)                0.019
    Asymmetrical pigmented follicular openings                                   20 (76.9)               0 (0.0)               <0.001
    Follicular obliteration                                                      10 (38.5)               0 (0.0)               <0.001
a
    This group included 15 solar lentigines, 12 seborrheic keratoses, six lichenoid keratoses, and two pigmented actinic keratoses.



Original Article | Dermatol Pract Concept. 2023;13(2):e2023101                                                                            3
                                     Table 2. 400x dermoscopy features of facial lesions.
                                                                                 LM/LMM                  Othera
                                                                                   N=26                   N=35
                                                                                   n(%)                   n(%)                  P-value
    Cell presence:
       Roundish melanocytes                                                      24 (92.3)               4 (11.4)               <0.001
       Dendritic melanocytes                                                     25 (96.2)               7 (20.0)               <0.001
       Roundish or dendritic Melanocytes                                         25 (96.2)               9 (25.7)               <0.001
       Keratinocytes                                                            26 (100.0)              33 (94.3)                0.503
       Melanophages                                                              15 (57.7)              11 (31.4)                0.066
    Melanocytes irregular in shape and size                                      18 (69.2)              10 (28.6)                0.002
    Melanocyte colour:
       Brown                                                                    26 (100.0)              10 (28.6)                0.503
       Violet/blue                                                                4 (15.4)               8 (22.9)                0.532
       Black                                                                       0 (0.0)               1 (2.9)                 1.000
    Melanocytes distribution:
    Irregular arrangement                                                        20 (76.9)               9 (25.7)               <0.001
    Out of focus bluish structureless areas                                      13 (50.0)              12 (34.3)                0.294
    Out of focus grey/brown structureless areas                                   8 (30.8)               9 (25.7)                0.775
    Vessels                                                                      16 (61.5)              20 (57.1)                0.796
    Vessels shape:
       Linear + arborizing                                                        7 (43.8)               6 (30.0)                0.493
       Irregular in shape                                                         8 (50.0)               6 (30.0)                0.307
    Hyperkeratotic roundish concentric structure                                   2 (7.7)              10 (28.6)                0.055
    Folliculotropism                                                             24 (92.3)               0 (0.0)                <0.001
a
    This group included 15 solar lentigines, 12 seborrheic keratoses, six lichenoid keratoses, and two pigmented actinic keratosis.




Figure 1. 20x dermoscopy (A), clinical (B) and 400x dermoscopy (C-F) images of a lentigo maligna. 400x dermoscopy shows dendritic
(red arrow) and roundish (yellow arrow) melanocytes and melanocytic invasion of a hair follicle (asterisk). Scale bar 100µm.




4                                                                               Original Article | Dermatol Pract Concept. 2023;13(2):e2023101
Figure 2. 20x dermoscopy (A), clinical (B) and 400x dermoscopy (C-E) images of a solar lentigo. 400x dermoscopy shows pigmented
­keratinocytes (white arrow) in the epidermis around hair follicles (asterisk). Scale bar 100µm.




for the differential diagnosis between LM/LMM and benign
                                                                 Conclusions
lesions. Folliculotropism of melanocytes was present in 24
LM/LMMs (92.3%, Figure 1) while it was absent in all be-         Conventional dermoscopy at 20x magnification can help
nign skin lesions analyzed (P < 0.001). Lastly, hyperkeratotic   the diagnosis of LM/LMM and our series found five criteria
roundish concentric structures were found in 10 benign skin      (demarcated borders, milia-like cysts/comedo-like openings,
lesions (28.6%) and 2 LM/LMMs (7.7%), with a P value just        annular-granular pattern/gray circles, asymmetric pigmented
above the threshold of statistical significance (P = 0.055).     follicular openings, and follicular obliteration) that could
                                                                 help the differential diagnosis in the monovariate analysis
Multivariate Analysis                                            [14,15].Our results agreed with a recent study that high-
The multivariate regression considered the following             lighted how 20x dermoscopic features suggestive of solar
variables: sharply demarcated borders, milia-like cysts          lentigo/flat seborrheic keratosis or pigmented actinic kerato-
/comedo-like openings, annular granular pattern/ gray cir-       sis can help to exclude the possibility of an LM/LMM [18].
cles, roundish melanocytes, melanocyte irregularity in shape     The presence of sharply demarcated borders, a typical fea-
and size, irregular arrangement of melanocyte distribution,      ture of solar lentigo/flat seborrheic keratosis, was the most
and follicular obliteration. Although asymmetrical pig-          relevant parameter to exclude LM/LMM in the multivariate
mented follicular openings, dendritic melanocytes, roundish      analysis (OR: 0.1, 95% CI 0.01-0.79, P = 0.038).
or dendritic melanocytes, and folliculotropism were statis-          Recently, it has been demonstrated that D400, a new
tically significant at univariate analysis, they were excluded   non-invasive skin imaging tool that can reveal pigmented
from multivariate analysis since their presence/absence al-      cells in the skin, could also help the clinical diagnosis of cu-
most perfectly explained the presence/absence of LM/LMM.         taneous melanoma, but no data on facial melanoma were
According to the stepwise procedure, roundish melanocytes        available [17]. Our study found that D400 could also have a
at 400x dermoscopy were more indicative of LM/LMM                role in the diagnosis of facial melanoma, namely LM/LMM.
(OR 49.25, 95% CI 8.75-513.2, P < 0.001), and sharply                According to our results shown in Table 2, we observed
demarcated borders at 20x dermoscopy were more indica-           that the presence of roundish and/or dendritic melanocytes
tive of not-LM/LMM lesion (OR 0.1, 95% CI 0.01-0.79,             in D400 was more frequently associated with LM/LMM
P = 0.038).                                                      than the other pigmented facial lesions (P < 0.001, Figure 1).




Original Article | Dermatol Pract Concept. 2023;13(2):e2023101                                                                 5
Notably, the presence of roundish melanocytes was highly           References
in favor of LM/LMM (OR 49.25, 95% CI 8.75-513.2, P <
0.001). Moreover, the irregular shape and size (P = 0.002)          1. Iannacone MR, Youlden DR, Baade PD, Aitken JF, Green
                                                                       AC. Melanoma incidence trends and survival in adoles-
and distribution of melanocytes (P < 0.001) in D400 were
                                                                       cents and young adults in Queensland, Australia. Int J Can-
also more frequent in LM/LMM.
                                                                       cer. 2015;136(3):603-609. DOI: 10.1002/ijc.28956. PMID:
    A distinctive feature of LM/LMM is the invasion of the             24806428. PMCID: PMC4277328.
follicular structures, which can be indirectly appreciated          2. Sacchetto L, Zanetti R, Comber H, et al. Trends in incidence
in conventional dermoscopy as pigmentation around hair                 of thick, thin and in situ melanoma in Europe. Eur J Cancer.
follicles [19]. As expected, in our series we found annular            2018;92:108-118. DOI: 10.1016/j.ejca.2017.12.024. PMID:
                                                                       29395684.
granular pattern/gray circles (P = 0.019) or asymmetrical
                                                                    3. Ferlay JSH, Bray F, et al. GLoBoCanN Cancer incidence and
pigmented follicular openings (P < 0.001) up to a complete
                                                                       mortality Worldwide: IARC CancerBase No. 10. Lyon, France:
follicular obliteration (P < 0.001) as 20x dermoscopic fea-            international agency for Research on Cancer. 2010. Available
tures associated with LM/LMM. However, as demonstrated                 from: http://globocan.iarc.fr (last accessed 1 December 2021).
by several studies, these dermoscopic features are not spe-         4. Rapporto AIOM-AIRT 2017. Available from: http://media.aiom.it/
cific of LM/LMM [20]. Our case series revealed that D400               userfiles/files/doc/documenti_scientifici/2017_numeri _del_­cancro.
                                                                       pdf. (last accessed 1 December 2021).
can directly show single melanocyte invasion of the hair
                                                                    5. Dabouz F, Barbe C, Lesage C, et al. Clinical and histological fea-
follicles increasing the diagnostic specificity for facial mela-
                                                                       tures of head and neck melanoma: a population-based study in
noma: almost all LM/LMMs and no other pigmented facial                 France. Br J Dermatol. 2015;172(3):707-715. DOI: 10.1111/
lesions had visible folliculotropism (P < 0.001) in our series         bjd.13489. PMID: 25333719.
(Figure 1).                                                         6. Robinson M, Primiero C, Guitera P, et al. Evidence-Based Clin-
    Vessel presence and out-of-focus bluish structureless              ical Practice Guidelines for the Management of Patients with
                                                                       Lentigo Maligna. Dermatology. 2020;236(2):111-116. DOI:
areas, features considered as predictive of melanoma with
                                                                       10.1159/000502470. PMID: 31639788.
D400 in our previous study, were not relevant for the iden-
                                                                    7. Lachiewicz AM, Berwick M, Wiggins CL, Thomas NE. Survival
tification of LM/LMM [17]. Neovascularization is probably
                                                                       differences between patients with scalp or neck melanoma and
less evident in pigmented superficial melanoma of LM/LMM               those with melanoma of other sites in the Surveillance, Epide-
subtype than in other MM and the presence of bluish struc-             miology, and End Results (SEER) program. Arch Dermatol.
tureless areas in non-melanoma lesions of our series could             2008;144(4):515-521. DOI: 10.1001/archderm.144.4.515.
be explained by regression features (aggregates of melano-             PMID: 18427046.
                                                                    8. International Agency for Research on Cancer (IARC) W. Can-
phages) mainly seen in lichenoid keratoses.
                                                                       cer incidence in five continents CI5plus: IARC CancerBase No
    The main limitation of this study is represented by the
                                                                       9. 2018. Available from: http://ci5.iarc.f r/CI5plus/Default.aspx
small sample and the fact that the acquisition and the eval-           (last accessed 1 December 2021).
uation of the images were dependent on the expertise of the         9. Lee KA, Nathan P. Cutaneous Melanoma - A Review of Sys-
investigators. In addition, correlation with histopathological         temic Therapies. Acta Derm Venereol. 2020;100(11):adv00141.
images and images of other new non-invasive imaging tech-              DOI: 10.2340/00015555-3496. PMID: 32346745. PMCID:
                                                                       PMC9189748.
niques such as RCM was lacking. If we compare D400 to
                                                                   10. J Jerant AF, Johnson JT, Sheridan CD, Caffrey TJ. Early de-
RCM, D400 has less concern of false-positive results given
                                                                       tection and treatment of skin cancer. Am Fam Physician.
by the presence of dendritic Langerhans cells in the epider-           2000;62(2):357-368, 375-6, 381-2. PMID: 10929700.
mis possibly mistaken for melanocytes under RCM and has            11. Tanaka M, Sawada M, Kobayashi K. Key points in dermo-
a lower cost. However, D400 can miss atypical melanocytes              scopic differentiation between lentigo maligna and solar
that are not heavily pigmented or deeper located and can               lentigo. J Dermatol. 2011;38(1):53-58. DOI: 10.1111/j.1346-
                                                                       8138.2010.01132.x. PMID: 21175756.
show large cells suggestive of atypical melanocytes when
                                                                   12. Stante M, Giorgi V, Stanganelli I, Alfaioli B, Carli P. Der-
multiple keratinocytes are superposed due to the lack of
                                                                       moscopy for early detection of facial lentigo maligna. Br
confocal sections.                                                     J Dermatol. 2005;152(2):361-364. DOI: 10.1111/j.1365-
    In conclusion, our study about the use of D400 for the             2133.2004.06328.x. PMID: 15727654.
diagnosis of facial lesions found that D400 can identify atyp-     13. Kasprzak JM, Xu YG. Diagnosis and management of lentigo ma-
ical melanocyte proliferation and folliculotropism that can            ligna: a review. Drugs Context. 2015;4:212281. DOI: 10.7573/
                                                                       dic.212281. PMID: 26082796. PMCID: PMC4453766.
help the diagnosis of LM/LMM together with conventional
                                                                   14. Cinotti E, Fiorani D, Labeille B, et al The integration of der-
dermoscopy data. Moreover, we could assume that D400
                                                                       moscopy and reflectance confocal microscopy improves the
could help to direct the choice of the more representative site        diagnosis of lentigo maligna. J Eur Acad Dermatol Venereol.
to perform a biopsy. Our preliminary observations should be            2019;33(10):e372-e374. DOI: 10.1111/jdv.15669. PMID:
confirmed by larger studies.                                           31074539.




6                                                                       Original Article | Dermatol Pract Concept. 2023;13(2):e2023101
15. Cinotti E, Labeille B, Debarbieux S, Cet al. Dermoscopy vs. re-         readers for lentigo maligna diagnosis. J Am Acad Dermatol.
    flectance confocal microscopy for the diagnosis of lentigo ma-          2021;84(2):381-389. DOI: 10.1016/j.jaad.2020.06.085. PMID:
    ligna. J Eur Acad Dermatol Venereol. 2018;32(8):1284-1291.              32592885.
    DOI: 10.1111/jdv.14791. PMID: 29341263.                             19. Dika E, Lambertini M, Patrizi A, et al. Folliculotropism in head
16. Cinotti E, Rossi R, Ferrara G, Tognetti L, Rubegni P, Perrot            and neck lentigo maligna and lentigo maligna melanoma. J Dtsch
    JL. Image Gallery: Super-high magnification dermoscopy can              Dermatol Ges. 2021;19(2):223-229. DOI: 10.1111/ddg.14311.
    identify pigmented cells: correlation with reflectance confocal         PMID: 33166059.
    microscopy. Br J Dermatol. 2019;181(1):e1. DOI: 10.1111/            20. Akay BN, Kocyigit P, Heper AO, Erdem C. Dermatoscopy
    bjd.17781. PMID: 31259403.                                              of flat pigmented facial lesions: diagnostic challenge be-
17. Cinotti E, Tognetti L, Campoli M, et al. Super-high magnification       tween pigmented actinic keratosis and lentigo maligna. Br J
    dermoscopy can aid the differential diagnosis between melanoma          Dermatol. 2010;163(6):1212-1217. DOI: 10.1111/j.1365-
    and atypical naevi. Clin Exp Dermatol. 2021;46(7):1216-1222.            2133.2010.10025.x. PMID: 21083845.
    DOI: 10.1111/ced.14566. PMID: 33486758.
18. Lallas A, Lallas K, Tschandl P, et al. The dermoscopic in-
    verse approach significantly improves the accuracy of human




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