10.5826/dpc.1401a36
Introduction: The term "atypical melanocytic nevus" (AMN) is used as a synonym for dysplastic nevus (DN) in clinical practice. Although the criteria for diagnosis of AMN/DN by the Agency for Research on Cancer helps to differentiate AMN/DN from common acquired nevi, they do not have high degrees of specificity, as they are similar to those used for the diagnosis of melanoma.
Objectives: In this retrospective study we evaluated the correlation and diagnostic concordance of dermoscopy, confocal microscopy, and histological examination in 50 AMN.
Methods: A graded scale was used to compare histological examination with dermoscopy and confocal microscopy. Low magnification histological images of only the central part of lesions were examined. This allowed histological diagnoses based almost exclusively on architectural criteria instead of simultaneously architectural and cytological, as in the global histological examination.
Results: Our data demonstrate that the diagnostic accuracy of dermoscopy and confocal microscopy diagnosis of the clinical aspects of AMN/DN as nevi or melanomas tends to be equivalent, being fair for nevi and excellent for melanomas. The total percentage of AMN suggested that the accuracy of confocal microscopy in the diagnosis of melanoma (86.7%) is greater than that of dermoscopy (73.3%).
Conclusions: This study demonstrated that diagnostic assessments of AMN/DN by dermoscopy and confocal microscopy are accurate and often coincide with those of histological examination and that their combined use helps to better manage and monitor these patients by facilitating early detection of melanomas and reducing unnecessary excisions of benign melanocytic lesions.
text/xml
2160-9381
3046
en
Giovanni Pellacani
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
melanoma
Dermoscopic, Histological, Confocal Microscopy Correlation of Atypical-Dysplastic Melanocytic Nevi 
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2024-01-31
2022-12-04
2024-01-31
2024-02-21
e2024036
Dermatol Pract Concept
Introduction: The term "atypical melanocytic nevus" (AMN) is used as a synonym for dysplastic nevus (DN) in clinical practice. Although the criteria for diagnosis of AMN/DN by the Agency for Research on Cancer helps to differentiate AMN/DN from common acquired nevi, they do not have high degrees of specificity, as they are similar to those used for the diagnosis of melanoma.
Objectives: In this retrospective study we evaluated the correlation and diagnostic concordance of dermoscopy, confocal microscopy, and histological examination in 50 AMN.
Methods: A graded scale was used to compare histological examination with dermoscopy and confocal microscopy. Low magnification histological images of only the central part of lesions were examined. This allowed histological diagnoses based almost exclusively on architectural criteria instead of simultaneously architectural and cytological, as in the global histological examination.
Results: Our data demonstrate that the diagnostic accuracy of dermoscopy and confocal microscopy diagnosis of the clinical aspects of AMN/DN as nevi or melanomas tends to be equivalent, being fair for nevi and excellent for melanomas. The total percentage of AMN suggested that the accuracy of confocal microscopy in the diagnosis of melanoma (86.7%) is greater than that of dermoscopy (73.3%).
Conclusions: This study demonstrated that diagnostic assessments of AMN/DN by dermoscopy and confocal microscopy are accurate and often coincide with those of histological examination and that their combined use helps to better manage and monitor these patients by facilitating early detection of melanomas and reducing unnecessary excisions of benign melanocytic lesions.
Giovanni Pellacani
2024/01/31
10.5826/dpc.1401a36
e2024036
Dermatology Unit, Department of Clinical Internal Anesthesiologic Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
2160-9381
melanoma
en
e2024036
Argenziano G, Mordente I, Ferrara G, Sgambato A, Annese P, Zalaudek I. Dermoscopic monitoring of melanocytic skin lesions: clinical outcome and patient compliance vary according to follow-up protocols. Br J Dermatol. 2008;159(2):331-336. DOI: 10.1111/j.1365-2133.2008.08649.x. PMID: 18510663.
Dermoscopic, Histological, Confocal Microscopy Correlation of Atypical-Dysplastic Melanocytic Nevi 
https://dpcj.org/index.php/dpc/article/download/3046/2418
 Dermoscopic, Histological, Confocal Microscopy
Correlation of Atypical-Dysplastic Melanocytic Nevi
            Carmen Cantisani1, Luca Ambrosio1, Emanuele Annessi1, Caterina Longo2,
         Francesca Farnetani2, Claudia Pezzini2, Alessandra Condorelli2, Giorgio Annessi3,
           Luca Reggiani Bonetti4, Stefania Guida5, Carlo Cota6, Antonella Tammaro7,
                               Camilla Chello1, Giovanni Pellacani1


1 Dermatology Unit, Department of Clinical Internal Anesthesiologic Cardiovascular Sciences, “Sapienza” University of Rome, Rome, Italy
2 Dermatology Unit, University of Modena and Reggio Emilia, Modena, Italy
3 Dermatopathology Unit, Istituto Dermopatico dell’Immacolata, IRCCS, Roma, Italy
4 Department of Diagnostic Clinic and Public Health Medicine University of Modena and Reggio Emilia, Italy
5 School of medicine Vita Salute San Raffaele University, Dermatology Clinic, IRCS San Raffaele Hospital, Milan, Italy
6 Genetic Research Molecular Biology and Dermopathology Unit San Gallicano Dermatology Unit, IRCCS, Rome Italy
7 NESMOS Dermatology Department, Sapienza University of Rome, Rome, Italy



Key words: atypical nevi, confocal microscopy, dermoscopy, dysplastic nevi, histopathology, melanoma
Citation: Cantisani C, Ambrosio L, Annessi E, et al. Dermoscopic, Histological, Confocal Microscopy Correlation of Atypical-Dysplastic
Melanocytic Nevi. Dermatol Pract Concept. 2024;14(1):e2024036. DOI: https://doi.org/10.5826/dpc.1401a36
Accepted: August 8, 2023; Published: January 2024
Copyright: ©2024 Cantisani 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: Carmen Cantisani, MD Prof, Dermatologist, UOC of Dermatology Policlinico Umberto I Hospital “Sapienza”
Medical School of Rome, Viale del Policlinico 155, Italy, 00161




  ABSTRACT             Introduction: The term “atypical melanocytic nevus” (AMN) is used as a synonym for dysplastic
                       nevus (DN) in clinical practice. Although the criteria for diagnosis of AMN/DN by the Agency for Re-
                       search on Cancer helps to differentiate AMN/DN from common acquired nevi, they do not have high
                       degrees of specificity, as they are similar to those used for the diagnosis of melanoma.
                       Objectives: In this retrospective study we evaluated the correlation and diagnostic concordance of
                       dermoscopy, confocal microscopy, and histological examination in 50 AMN.
                       Methods: A graded scale was used to compare histological examination with dermoscopy and confo-
                       cal microscopy. Low magnification histological images of only the central part of lesions were exam-
                       ined. This allowed histological diagnoses based almost exclusively on architectural criteria instead of
                       simultaneously architectural and cytological, as in the global histological examination.




Original Article | Dermatol Pract Concept. 2024;14(1):e2024036                                                                            1
                      Results: Our data demonstrate that the diagnostic accuracy of dermoscopy and confocal microsco-
                      py diagnosis of the clinical aspects of AMN/DN as nevi or melanomas tends to be equivalent, being
                      fair for nevi and excellent for melanomas. The total percentage of AMN suggested that the accuracy
                      of confocal microscopy in the diagnosis of melanoma (86.7%) is greater than that of dermoscopy
                      (73.3%).
                      Conclusions: This study demonstrated that diagnostic assessments of AMN/DN by dermoscopy and
                      confocal microscopy are accurate and often coincide with those of histological examination and that
                      their combined use helps to better manage and monitor these patients by facilitating early detection of
                      melanomas and reducing unnecessary excisions of benign melanocytic lesions.




Introduction                                                        lamellar and concentric fibroplasia and lymphocyte infiltrate
                                                                    in the papillary dermis [4,5]. Cytological atypia is charac-
Dysplastic nevi (DN) are acquired melanocytic nevi that,            terized by the focal presence of melanocytes with increased
compared to common nevi, appear larger and less symmet-             nuclear size, pleomorphic nuclei, hyperchromatic nuclei with
rical in their configuration. For this reason, the clinical term    chromatin thickening and prominent nucleoli. Although
“atypical melanocytic nevus” (AMN) is used as a synonym             there is some variability by even experienced dermatopathol-
for dysplastic nevus (ND) in clinical practice. In 1990 the In-     ogists in applying the criteria of histological dysplasia, nu-
ternational Agency for Research on Cancer established the           merous studies have demonstrated significant intra-observer
following criteria for the clinical diagnosis of AMN/DN: all        and inter-observer reproducibility in the histological diagno-
AMN/DN have a macular component, at least in one area               sis of dysplastic nevus and thus good reliability in the use of
of the lesion. To this criterion should be added at least three     these histological criteria [6,7]. In order to identify classes
more of the following: size > 5 mm, fuzzy lesion, border not        of patients with different risk of melanoma, attempts have
well defined, color variability, irregularity of lesion contour,    also been made to classify dysplastic nevi into two or more
erythema [1,2]. Often the nevus has a central raised area sur-      histological grades (mild, moderate and severe dysplasia).
rounded by a macular component giving a ‘fried egg’ or ‘tar-        Although many authors have proposed various grading
get’ appearance. Although these criteria help in differentiating    schemes, few studies have addressed the issue of diagnostic
AMN/DN from common acquired nevi, they do not have a                reproducibility and melanoma risk associated with histolog-
high degree of specificity as they are very similar to those used   ical dysplasia grade [8,9]. These studies have shown both
for the diagnosis of melanoma. Generally, with many excep-          poor inter-observer reproducibility of histological criteria
tions, the clinical difference between an AMN/DN and a mel-         for mild, moderate and severe dysplasia grades and a lack
anoma depends on the extent of these criteria: the more the         of significant correlation between atypia grades and mela-
lesion has them, the more likely the diagnosis of melanoma.         noma risk.
    Histologically, a nevus is dysplastic when it simultane-           Currently, most authors agree that the diagnosis of
ously presents an architectural disorder and cytological            AMN/DN is clinic-histological, ie it requires the simulta-
atypia [3]. The typical common junctional melanocytic ne-           neous presence of the criteria for clinical and histological
vus is formed by vertically oriented thecae of melanocytes          dysplasia [10-12]. Other research, instead, have highlighted
located at the apex of the epidermal ridges. Architectural dis-     a significant presence of histological dysplasia in nevi lack-
order means a deviation from this histological pattern in a         ing clinical dysplasia and therefore a limited specificity and
lesion that is generally larger than the stereotypical common       sensitivity of the clinical criteria for dysplastic nevus when
acquired melanocytic nevus. In particular, architectural dis-       compared with the histological ones [13]. The possible lack
order is characterized by the presence of a junctional “shoul-      of good clinical-histological correlation of the criteria for
der” extending laterally to the dermal component, thecae of         identifying dysplastic nevus casts some doubt on the real ex-
melanocytes varying in shape and size, thecae of melano-            istence of AMN/DN as a clinicopathological entity. Added
cytes oriented horizontally at the dermo-epidermal junction         to this is the fact that no study to date has demonstrated the
bridging adjacent epidermal ridges, poorly cohesive intraepi-       value of histological dysplasia as an independent risk factor
dermal melanocytic thecae, presence of a greater density of         for melanoma. It follows that, at present, AMN/DN is only
single melanocytes at the dermo-epidermal junction (more            of relevance on the clinical side. In practice, only the clini-
melanocytes than keratinocytes in an area > 1 mm2), pres-           cal presence of nevi with ND/AMN features (independent of
ence of a few single melanocytes in the suprabasal layer of         their histological aspects) is to be considered a risk factor for
the epidermis (typically fewer in number than in melanoma),         melanoma independent of other factors such as total number


2                                                                       Original Article | Dermatol Pract Concept. 2024;14(1):e2024036
of nevi, family history of melanoma, phototype and expo-            Department of Dermatology of the University of Modena
sure to ultraviolet radiation.                                      and Reggio Emilia were available of all lesions.
    As mentioned, AMN/DN often have clinical features
overlapping with melanoma in situ and thin melanoma                 Dermoscopic Study
(SSM). From a prevention and patient care point of view, it         Dermoscopic images were obtained through the use of a
is therefore essential to use all the tools at our disposal to be   polarized light dermoscope (DermLite Photo 3Gen LLC).
able to make the best differential diagnosis of these lesions.      All dermoscopic images were analyzed by an expert in der-
    Among the most easily used non-invasive diagnostic              moscopy unaware of both the histological diagnosis and any
methods is dermoscopy, which allows the visualization of            clinical information, and confocal microscopy referable to the
structural features of pigmented lesions that cannot be ap-         lesions under examination. Using the pattern analysis method
preciated by simple clinical observation [14-16]. However,          each lesion was classified according to a graded scale as: -3
most authors agree that currently no qualitative parameters         nevus certain; -2 nevus probable; -1 nevus possible; +1 mela-
have been discovered or semi-quantitative systems devised           noma possible; +2 melanoma probable; +3 melanoma certain.
that can accurately and reproducibly differentiate AMN/DN
from melanoma in situ or melanoma in its early growth phase.        Confocal Microscopy Study
    In vivo reflectance confocal microscopy (RCM) is a
                                                                    Images were acquired through the use of a laser scanning
non-invasive technology that allows real-time visualiza-
                                                                    confocal microscope (Vivascope 1500; MAVIG GmBH). The
tion of skin structures at a resolution similar to histology.
                                                                    mosaics were acquired at three levels corresponding to the
Overall, the diagnostic accuracy of RCM for melanoma has
                                                                    superficial layer of the epidermis (stratum spinosum and
been shown to be superior to that of dermoscopy [17]. The
                                                                    stratum granulosum), at the level of the dermo-epidermal
RCM has also been shown to identify characteristic fea-
                                                                    junction and at the level of the papillary dermis.
tures of AMN/DN [18]. The basic histopathological criteria
                                                                       For our study, mosaic images showing the dermo-
for histological dysplasia have precise correlates in confo-
                                                                    epidermal junction of individual lesions were examined.
cal microscopy. In this regard, a simple algorithm has been
                                                                    In particular, only the central portion of each image corre-
proposed to differentiate AMN/DN from common acquired
                                                                    sponding to a lesion area of approximately 3 mm × 3 mm
melanocytic nevi and melanoma. The possibility of recog-
                                                                    was cut out and evaluated.
nizing histological dysplasia in vivo can lead to the correct
                                                                       The images of each individual lesion were examined by
removal of lesions most at risk for melanoma. RCM can
                                                                    a confocal microscopy expert who was kept unaware of
complement the histopathological report by improving the
                                                                    both the global histological diagnosis and any other clini-
distinction between melanoma and AMN/DN.
                                                                    cal and dermoscopic information referable to the lesions
                                                                    under study. Using the parameters introduced by Pellacani
Objectives                                                          and collaborators, each lesion was classified according to a
                                                                    graded scale as: -3 nevus certain; -2 nevus probable; -1 n
                                                                                                                             ­ evus
The present study is a retrospective clinical case-control          possible; +1 melanoma possible; +2 melanoma probable;
study based on microscopic and instrumental images and              +3 melanoma certain [22].
aims to evaluate the accuracy, correlation and diagnostic
concordance of dermoscopic examination, confocal micros-            Histopathological Study
copy and histological examination in a population of AMN/
                                                                    For each lesion, a histological image of 10x magnifica-
DN in order to improve the clinical behavior and diagnosis
                                                                    tion was scanned using a digital histological slide scanner
of atypical melanocytic lesions.
                                                                    (D-sight, Menarini SpA). Subsequently, in order to analyze
                                                                    approximately the same area of the lesion as the one ex-
Methods                                                             amined by confocal microscopy, a portion of the scanned
                                                                    histological image representing approximately the central 3
Study Population                                                    mm of the lesion was cut out from each scanned histological
Atypical melanocytic lesions excised from 50 patients be-           image. At this point, the images were submitted to an expert
tween 2018 and 2020 were studied to rule out melanoma.              dermatopathologist for examination. Obviously, the viewing
All lesions were selected as having the clinical features of        of partial and low-magnification histological images of the
AMN/DN, ie appearing as barely palpable macules or                  lesions allowed a histological evaluation based mainly on ar-
plaques, larger than 0.5 cm in diameter and having at least         chitectural parameters rather than cytological ones. This was
two of the following criteria: shaded border, color variabil-       intended to make the diagnostic comparison between histo-
ity, irregularity of lesion margins and erythema. Both der-         logical images and those of dermoscopy and confocal mi-
moscopic and confocal microscopy images acquired at the             croscopy, which are known to base their diagnostic capacity


Original Article | Dermatol Pract Concept. 2024;14(1):e2024036                                                                   3
mainly on architectural criteria, more homogeneous. There-         0 denotes agreement that can only be explained by chance,
fore, the dermatopathologist, on the basis of the histological     a value of +1 means absolute agreement while a negative
criteria described in the literature [19,20] and in the absence    value implies complete disagreement. Intermediate κ values
of the histological diagnosis and of any clinical, dermoscopic     of denote non-random agreement as follows: less than 0.20
and confocal microscopy information on the lesions under           negligible; 0.20-0.40 poor; 0.40-0.60 moderate; 0.60-0.80
examination, was called to classify each lesion using the fol-     good; greater than 0.80 excellent.
lowing gradation: -3 nevus certain; -2 nevus probable; -1 ne-
vus possible; +1 melanoma possible; +2 melanoma probable;
                                                                   Results
+3 melanoma certain [19,20].
                                                                   Of the 50 patients enrolled, 42% were male and 58% fe-
Statistical Study                                                  male; the mean age was 47 years; 46% of the lesions were
The statistical study was conducted by deriving the rela-          located on the trunk, 27% on the lower limbs; 21% on the
tive and absolute frequencies of the various dermoscopic,          upper limbs and 6% in the head and neck region.
confocal microscopy and histological diagnoses obtained by            Of the 50 lesions, 20 were histologically diagnosed as
applying the grading system described above to our popu-           melanocytic nevi, and 30 as melanomas (4 melanomas in
lation of AMN/DN.                                                  situ, 24 superficial spreading melanomas of Breslow thick-
    The correlation coefficient (Spearman Rho) was also            ness less than one millimeter and 2 melanomas arising on
used to assess the presence of any correlations between the        melanocytic nevus). In this study, the global histological eval-
dermoscopic, confocal microscopy and histological diagnos-         uation ie based on architectural and cytological criteria was
tic grading systems used in this study.                            considered as the diagnostic gold standard.
    Finally, the concordance between the dermoscopic diag-            Tables 1-3 show the absolute and relative frequencies of
nostic grading, confocal microscopy and histological grading       the individual diagnostic grades found by dermoscopic, con-
systems was calculated through Cohen κ value. A κ value of         focal microscopic and histological examination compared



                  Table 1. Absolute and relative frequencies of individual diagnostic grade
                                   values on dermoscopic examination.
    Global Histological                              Dermoscopic diagnostic grading
                                                                                                                          Total
        Diagnosis                 -3           -2            -1             1               2                3
 Nevus n°(%)                   1(5%)        5(25%)        5(25%)         4(20%)          4(20%)           1(5%)        20(100%)
 Melanoma n°(%)                 0(%)         0(%)          0(%)         8(26,7%)       14(46,7%)        8(26,7%)       30(100%)
 Total n°(%)                   1(2%)        5(10%)        5(10%)        12(24%)         18(36%)          9(18%)        50(100%)




                  Table 2. Absolute and relative frequencies of individual diagnostic grade
                               values on confocal microscopy examination.
    Global Histological                                 Confocal diagnostic grading
                                                                                                                          Total
        Diagnosis                 -3           -2            -1             1               2                3
 Nevus n°(%)                  4(20%)        3(15%)        3(15%)         5(25%)          3(15%)          2(10%)        20(100%)
 Melanoma n°(%)                 0(%)         0(%)          0(%)         4(13,3%)       11(36,7%)         15(50%)        30(100%
 Total n°(%)                   4(8%)        3(6%)          3(6%)         9(18%)         14(28%)          17(34%)       50(100%)




                  Table 3. Absolute and relative frequencies of individual diagnostic grade
                                    values on histological examination.
    Global Histological                               Histological diagnostic grading
                                                                                                                          Total
        Diagnosis                 -3           -2            -1             1               2                3
 Nevus n°(%)                  3(15%)        6(30%)        2(10%)         7(35%)          2(10%)           0(0%)        20(100%)
 Melanoma n°(%)                 0(%)         0(%)          0(%)           0(%)         11(36,7%)        19(63,3%)      30(100%)
 Total n°(%)                   3(6%)        6(12%)         2(4%)         7(14%)         13(26%)          19(38%)       50(100%)


4                                                                      Original Article | Dermatol Pract Concept. 2024;14(1):e2024036
with the global histological diagnoses. On dermoscopic ex-              nevi were considered as possible melanoma (grade +1) and 2
amination, of 20 lesions with a histological diagnosis of ne-           nevi probable melanoma (grade +2), respectively.
vus, 11 were graded -3, -2 and -1 and therefore classified as               In order to facilitate the interpretation of the data, we
nevi and 9 (grades +1, +2 and +3) as possible or probable               then converted the results into a three-grade system called
melanoma. In contrast, all lesions with a histological diag-            -1, 0, +1, which was created on the basis of the degree
nosis of melanoma were also dermoscopically interpreted                 of diagnostic certainty. In grade -1 (very high probabil-
as melanoma (grade +1, 8 cases; grade +2, 14 cases; grade               ity of nevus diagnosis) we grouped the cases previously
+3, 8 cases). Similarly, confocal microscopy correctly clas-            classified as -3 and -2; in grade +1 (very high probability
sified all cases with a histological diagnosis of melanoma as           of melanoma diagnosis) we included all the cases clas-
melanoma (grade +1, 4 cases; grade +2, 11 cases; grade +3,              sified as +2 and +3; finally, in grade 0 (cases with un-
15 cases). Furthermore, confocal microscopy evaluated 50%               certain diagnosis between nevus/melanoma) we included
of the AMN/DNs in our study with histological diagnosis                 the cases diagnosed as -1 and +1. This subdivision shows
of nevus as benign lesions and the other 50% as possible                how the percentage of cases graded as uncertain (grade
or probable melanoma. Finally, the predominantly architec-              0) progressively decreases from 34% with dermoscopic
tural histological examination also correctly interpreted all           examination, to 24% with confocal microscopy, to 18%
lesions with histological diagnosis of melanoma, whereas 7              with histological examination (Figures 1-4). Spearman




     Figure 1. Good correlation between diagnostic grading with dermoscopy, confocal microscopy and histology. (A) AMN/DN with
     nevus histologic diagnosis. (B) Dermoscopic diagnosis: -3 (nevus certain). (C) Confocal microscopy diagnosis: -2 (nevus probable).
     (D)) histologic diagnosis: -3 (nevus certain).


Original Article | Dermatol Pract Concept. 2024;14(1):e2024036                                                                            5
Figure 2. Disagreement between confocal diagnosis with dermoscopic and histologic ones. (A) AMN/DN with nevus histologic diagnosis.
(B) Dermoscopic diagnosis: -1 (nevus possible). (C) Confocal microscopy diagnosis: +2 (melanoma probable). (D) histologic diagnosis: -1
(nevus possible).




analysis showed a statistically significant correlation be-          Conclusions
tween both the dermoscopic and confocal microscopy di-
agnostic grading system (ρ= 0.584, P < 0.001), between               In this study we evaluated the accuracy of the main meth-
dermoscopy and histology ((ρ= 0.600, p < 0.001) and also             ods available for the diagnosis of melanocytic lesions in a
between confocal microscopy and ­histology (ρ= 0.707,                population of clinically doubtful lesions. We also looked for
P < 0.001).                                                          possible correlation and diagnostic concordance between the
    Calculation of the agreement between the diagnoses               different methods. The dermoscopic, confocal microscopic
made using our grading system gave a statistical value of            and histological diagnoses were graded according to the
0.104 (agreement between dermoscopy and confocal mi-                 degree of diagnostic certainty as follows: nevus certain (-3);
croscopy), 0.162 (agreement between dermoscopy and his-              nevus probable (-2); nevus possible (-1); melanoma possible
tological examination EIa) and 0.314 (agreement between              (+1); melanoma probable (+2); melanoma certain (+3). This
confocal microscopy and histological examination).                   made it possible to evaluate the correlations between the



6                                                                         Original Article | Dermatol Pract Concept. 2024;14(1):e2024036
Figure 3. Disagreement between dermoscopic diagnosis with confocal and histologic ones. (A) AMN/DN with nevus histologic diagnosis.
(B) Dermoscopic diagnosis: -1 (nevus possible). (C) Confocal microscopy diagnosis: +2 (melanoma probable). (D) Histologic diagnosis: +1
(melanoma possible).




diagnostic methods in a very detailed way. In addition, it was       the correlation between the different methods. Examination
decided to use histological images taken at low magnification        of the absolute and relative frequencies of the different diag-
and representing only the central part of the lesion exam-           nostic grades (Tables 1-3) shows that the dermoscopic and
ined. This allowed histological diagnoses to be based almost         histological examination were able to correctly diagnose as
exclusively on architectural criteria, rather than on both           nevi 55% (N = 11) of the lesions with clinical features of
architectural and cytological criteria as in the global histo-       AMN/DN, compared to 50% (No = 10) of the confocal mi-
logical examination. In practice, by removing the cytological        croscopic examination. On the other hand, only 5% (N =1),
details from the histological image analysis, the histological       10% (N = 2) and 0% (N = 0) of lesions with histological di-
classification of lesions based on architectural criteria alone      agnosis of nevus were considered as definite melanoma (+3)
was brought into line with that of dermoscopy and confocal           by dermoscopy, confocal microscopy and histological exam-
microscopy, which are also predominantly based on archi-             ination respectively. It should also be noted that no lesion
tectural criteria, thus allowing a more reliable assessment of       with a histological diagnosis of melanoma was classified as a



Original Article | Dermatol Pract Concept. 2024;14(1):e2024036                                                                       7
Figure 4. Good correlation between dermoscopic, confocal and histologic diagnosis. (A) AMN/DN with melanoma histologic diagnosis.
(B) Dermoscopic diagnosis: +3 (melanoma certain). (C) confocal microscopy diagnosis: +3 (melanoma certain). (D) histologic diagnosis: +3
(melanoma certain).


nevus by any of the three methods. Taken together, these data         also classified some lesions as suspicious, but at a lower rate
suggest, firstly, that even a histological examination based          than dermoscopy and confocal microscopy, and all suspi-
almost exclusively on architectural aspects can correctly             cious lesions were found to be nevi on total histology.
diagnose lesions presenting clinically as AMN/DN as mela-                 The results of the Spearman test showed a statistically
noma. Secondly, the diagnostic accuracy of both dermoscopy            significant correlation between the dermoscopic and confo-
and confocal microscopy in correctly diagnosing lesions with          cal microscopy diagnostic grading system, between the der-
clinical aspects of AMN/DN as nevi or melanoma tends to               moscopic and histological grading system and between the
be equivalent, being fair for nevi and excellent for melanoma         confocal microscopy and histological grading system. This
Finally, architectural histology leaves doubt in 45% of the           suggests that the combination of dermoscopic and confocal
nevi, whereas it leaves none for melanoma, as all melanomas           examination can provide a good indication of the architec-
were correctly diagnosed as such. Taken together, these data          tural substrate of the lesion being examined.
indicate that all three methods for AMN/DN examination                    Finally, Cohen test showed poor agreement between the
detect cases in which the diagnosis is uncertain. Histology           dermoscopic and histological diagnostic grading system.



8                                                                         Original Article | Dermatol Pract Concept. 2024;14(1):e2024036
Better agreement, although not high, was observed between            and effort required to perform and periodically repeat total
confocal microscopy and histological examination It is note-         body mapping and digital dermoscopic monitoring, one must
worthy that all discordant cases were found to be melano-            rely on the patient compliance, which must be maintained
cytic nevi on global histology. It follows that there appears to     throughout life (estimated at less than 30% for 12-month
be good diagnostic agreement between the different methods           follow-ups), especially given the long time period [24].
when limited to the diagnosis of melanoma.                           Therefore, the ultimate benefit of being able to predict and
    Overall, this study shows if a lesion is classified as a defi-   intervene in possible precursors could be effective in making
nite/probable nevus or definite/probable melanoma by der-            the surveillance and prevention system simpler and less bur-
moscopy or confocal microscopy, there is a high probability          densome, both in terms of clinical and economic burden. Of
that this lesion will also be diagnosed as a nevus or melanoma       course, the scientific approach obliges us to consider the null
by histology. However, the correlation between dermoscopic           hypothesis, ie that melanoma does not arise through a process
and histological diagnosis, although good, is lower than that        of evolutionary stages, but from a single clonal expanding
between confocal microscopy and histology. From a prog-              cell, generating a random effect of appearance from healthy
nostic point of view, we have seen how crucial it is to de-          skin or on a melanocytic lesion. In such a case, it would be
tect melanoma in its early growth phase and how this can be          useful to orient the screening system towards whole-body
very difficult in patients with a high number of melanocytic         imaging systems, possibly combined with automatic systems
nevi and, in particular, AMN/DN with clinical features very          for identifying variations/new lesions. In conclusion, the com-
similar to those of melanoma. In the past, when the clinical         bined use of dermoscopic and confocal microscopic exam-
diagnosis was in doubt, many lesions were surgically removed         ination in subjects with AMN/DN allows better management
that later proved to be simple melanocytic nevi on histological      and monitoring of these patients, favoring early detection of
examination, which in retrospect was unnecessary. This study,        possible melanoma and a significant reduction in unnecessary
together with others in the literature, by showing a remark-         excision of benign melanocytic lesions.
able correlation between dermoscopic, confocal microscopic
and histological diagnoses, demonstrates that non-invasive
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