10.5826/dpc.1302a80
Introduction:Diagnosis of melanoma can be sometimes very difficult because of its phenotypic and histological heterogeneity.Difficult-to-diagnose melanoma can be represented by mucosal melanoma, pink lesions, amelanotic melanoma (amelanotic lentigo maligna, amelanotic acral melanoma, desmoplastic melanoma), melanoma arising on sun-damaged facial skin, and “featureless melanoma”.Objective:The aim of the study was to improve the identification of featureless melanoma (scoring 0-2 according to 7-point-checklist)describing the variegated dermoscopical features and their histo-pathological correlation.Methods:Study samples included all melanomas excised based on clinical and/or dermoscopic findings in the period between January 2017 and April 2021.Before excisional biopsy, all lesions were recorded by means of digital dermoscopy at the department of Dermatology.Only lesions with a diagnosis of melanoma and a high quality of dermoscopic images were included in this study. After clinical and dermoscopic evaluation of 7-point checklist score, single dermoscopic and histological features were considered for lesions with a score of 2 or lower and a diagnosis of melanoma (corresponding to dermoscopic featureless melanoma).Results:A total of 691 melanomas fulfilled inclusion criteria and were retrieved from the database. The 7-point checklist evaluation identified 19 “negative-featureless” melanoma.The 100% of the lesions with score 1 showed a globular pattern. Conlusions:Dermoscopy is still the best diagnostic method for melanoma. The 7-point checklist provides a simplification of standard pattern analysis because of the algorithm based on a scoring system and the lower number of features to recognize. In the daily practice it is more comfortable for many clinicians to keep in mind a list of principles that may help in the decision.
text/xml
2160-9381
2635
en
Giovanni Pellacani
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
difficult featureless melanoma
Identification of Novel Dermoscopic Patterns for “Featureless Melanoma”: Clinical-Pathological Correlation
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-04-29
2022-06-06
2023-04-29
2023-05-31
e2023080
Dermatol Pract Concept
Introduction:Diagnosis of melanoma can be sometimes very difficult because of its phenotypic and histological heterogeneity.Difficult-to-diagnose melanoma can be represented by mucosal melanoma, pink lesions, amelanotic melanoma (amelanotic lentigo maligna, amelanotic acral melanoma, desmoplastic melanoma), melanoma arising on sun-damaged facial skin, and “featureless melanoma”.Objective:The aim of the study was to improve the identification of featureless melanoma (scoring 0-2 according to 7-point-checklist)describing the variegated dermoscopical features and their histo-pathological correlation.Methods:Study samples included all melanomas excised based on clinical and/or dermoscopic findings in the period between January 2017 and April 2021.Before excisional biopsy, all lesions were recorded by means of digital dermoscopy at the department of Dermatology.Only lesions with a diagnosis of melanoma and a high quality of dermoscopic images were included in this study. After clinical and dermoscopic evaluation of 7-point checklist score, single dermoscopic and histological features were considered for lesions with a score of 2 or lower and a diagnosis of melanoma (corresponding to dermoscopic featureless melanoma).Results:A total of 691 melanomas fulfilled inclusion criteria and were retrieved from the database. The 7-point checklist evaluation identified 19 “negative-featureless” melanoma.The 100% of the lesions with score 1 showed a globular pattern. Conlusions:Dermoscopy is still the best diagnostic method for melanoma. The 7-point checklist provides a simplification of standard pattern analysis because of the algorithm based on a scoring system and the lower number of features to recognize. In the daily practice it is more comfortable for many clinicians to keep in mind a list of principles that may help in the decision.
Giovanni Pellacani
2023/04/29
10.5826/dpc.1302a80
e2023080
UOC of Dermatology, Umberto I hospital Sapienza Medical School, Rome, Italy
2160-9381
difficult featureless melanoma
en
e2023080
Argenziano G, Zalaudek I, Ferrara G et al. Dermoscopy features of melanoma incognito: Indications for biopsy. Journal of the American Academy of Dermatology 56, 508–513 (2007).
Identification of Novel Dermoscopic Patterns for “Featureless Melanoma”: Clinical-Pathological Correlation
https://dpcj.org/index.php/dpc/article/download/2635/2056
     Identification of Novel Dermoscopic Patterns
  for “Featureless Melanoma”: Clinical-Pathological
                       Correlation
            Salvatore Lampitelli1, Carmen Cantisani1, Federica Rega1, Camilla Chello1,2,
                           Francesca Farnetani2, Giovanni Pellacani1,2


1 UOC of Dermatology, Umberto I Hospital, Sapienza Medical School of Rome, Rome, Italy
2 Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy



Key words: difficult featureless melanoma, 7-point checklist, dermoscopy
Citation: Lampitelli S, Cantisani C, Rega F, Chello C, Farnetani F, Pellacani G. Identification of Novel Dermoscopic Patterns for
“Featureless Melanoma”: Clinical-Pathological Correlation. Dermatol Pract Concept. 2023;13(2):e2023080. DOI: https://doi.org/10.5826/
dpc.1302a80
Accepted: September 15, 2022; Published: April 2023
Copyright: ©2023 Lampitelli 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, UOC of Dermatology, Umberto I Hospital, Sapienza Medical School of Rome viale del
Policlinico 155, 00161 Rome Italy. tel: +39-0649976993 Email: c.cantisani@policlinicoumberto1.it; carmencantisanister@gmail.com




  ABSTRACT             Introduction: Diagnosis of melanoma can be very difficult because of its phenotypic and histolog-
                       ical heterogeneity. Difficult-to-diagnose melanoma can be represented by mucosal melanoma, pink
                       lesions, amelanotic melanoma (amelanotic lentigo maligna, amelanotic acral melanoma, desmoplastic
                       ­melanoma), melanoma arising on sun-damaged facial skin, and “featureless melanoma”.
                       Objectives: The aim of the study was to improve the identification of featureless melanoma
                       ­(scoring 0-2 according to the 7-point-checklist) describing the variegated dermoscopic features
                        and their histopathological correlation.
                       Methods: Study samples included all melanomas excised based on clinical and/or dermoscopic
                       ­findings in the period between January 2017 and April 2021. Before excisional biopsy, all lesions were
                        recorded by means of digital dermoscopy at the department of Dermatology. Only lesions with a diag-
                        nosis of melanoma and a high quality of dermoscopic images were included in this study. After clinical
                        and dermoscopic evaluation of 7-point checklist score, single dermoscopic and histological features
                        were considered for lesions with a score of 2 or lower and a diagnosis of melanoma (corresponding to
                        dermoscopic featureless melanoma).
                       Results: A total of 691 melanomas fulfilled inclusion criteria and were retrieved from the database.
                       The 7-point checklist evaluation identified 19 “negative-featureless” melanoma. The 100% of the
                       lesions with score 1 showed a globular pattern.




Original Article | Dermatol Pract Concept. 2023;13(2):e2023080                                                                       1
                     Conclusions: Dermoscopy is still the best diagnostic method for melanoma. The 7-point checklist pro-
                     vides a simplification of standard pattern analysis because of the algorithm based on a scoring system
                     and the lower number of features to recognize. In the daily practice it is more comfortable for many
                     clinicians to keep in mind a list of principles that may help in the decision.




Introduction                                                       amelanotic when there is a clinically and dermoscopically
                                                                   lack of pigmentation with melanin in less than 5% of tumor
Melanoma                                                           cells on histological examination [5].
Melanoma is one of the most aggressive forms of malig-                Any clinical subtypes of cutaneous melanoma may be
nant skin cancer deriving from altered and atypical neural         amelanotic, considering the desmoplastic melanoma as the
crest-derived melanocytes principally localized in the hair        most frequent type and the subungual site the most com-
follicles and in the basal layer of the epidermidis, and along     mon localization. Desmoplastic melanoma is a rare subtype
the meninges, choroid, and mucosal surfaces too. It accounts       with a nodular or a scar-like appearance. A primarily dermal
about 3% of the overall skin cancers diagnosed each year           component of spindle cells represents the main histological
and can develop from benign nevomelanocytic lesions, or,           finding. Most frequent in Caucasian people aged sixty to
more frequently, from normal-appearing skin, as result of a        seventy years and in sun-exposed areas of head and neck
complex interplay of genetic, environmental, and constitu-         region. Desmoplastic melanoma is more likely a sarcoma,
tional elements [1-3]. The worldwide incidence of cutaneous        considering the local aggressive biological behavior and the
melanoma has been growing annually with a very rapid rate          predisposition for local and visceral growth [3].
                       th
placing itself as the 15 most common tumor globally [2].              Pink lesions often represent a challenging diagnosis for
    The most important predictive prognostic factor is the         the absence of the identifiable peculiar characteristics using
type of growth. The radial growth phase (RGP), typical of          conventional methods, for example, epiluminescence micros-
melanoma in situ, defines a disease which is still localized and   copy. They constitute a very wide and heterogeneous group
restricted to the epidermidis, above the dermal-epidermal          of skin lesions of inflammatory and/or benign/malignant
junction showing a pagetoid spread within the skin. The            neoplastic origin [7]. Dermoscopy is still far from an accu-
vertical growth phase (VGP), further classified into an early      rate diagnosis about pink lesions, considering a rapid identi-
and a late stage, is characterized by the presence of dermal       fication crucial in the case of amelanotic melanoma or, even
tumoral nests, extending, sometimes, into subcutaneous fat.        worse, nodular amelanotic malignant melanoma. In these
                                                                   cases, particular dermoscopy findings include an irregular
Difficult Melanomas                                                shaped vascularization (linear, dotted, or globular vessels
One of the hardest challenges is the amelanotic melanoma           having an irregular distribution), whitish/depigmented areas,
occurring in about 2% of all malignant melanomas. It is            and ulceration [7].
more frequent in red hair patients with skin type I, freckles,        Primary mucosal melanoma was first described in 1856
a sun-sensitive phenotype, a previous history of amelanotic        by Weber et al [8]. Nowadays, despite its rarity, mucosal
melanoma or lack of naevi on the back [4,5]. In 1999 Koch          melanoma is of great interest because of its worse prognosis
et al defined the amelanotic melanoma as “the great mas-           compared to cutaneous subtype. Overall, only 0.8%-3.7%
querader” referring to the lack of the clinical hallmark of        are mucosal melanomas and, contrary to the recent grow-
cutaneous melanoma, that is the presence of several amounts        ing incidence of cutaneous melanoma, its incidence tends to
of melanic pigment within the tumor, determining misdi-            stay stable [9]. No association to any viral infections (human
agnoses [6]. Amelanotic melanoma may be confused with              herpes viruses, human papilloma viruses, and polyomavirus),
different benign (intradermal naevus, seborrheic keratosis,        ultraviolet (UV) radiation exposure or racial differences. Its
eczema, actinic keratosis, granuloma annulare, pyogenic            etio-pathogenesis remains unclear. Contrary to cutaneous mel-
granuloma, verruca vulgaris, naevus depigmentosus, scar,           anoma, C-KIT is overexpressed in about 80% of mucosal mel-
dermatofibroma, lymphocytoma cutis) and malignant (basal           anomas [9]. Mucosal melanoma can be localized within the
cell carcinoma, Merkel cell carcinoma, Bowen disease, kera-        mucosal membranes of the gastrointestinal, respiratory, and
toacanthoma, atypical fibroxanthoma, extramammary Paget            genitourinary tract. Head and neck are the most common an-
disease, malignant fibrous histiocytoma, malignant schwan-         atomic sites, in which the prognosis is believed to be better [9].
noma, squamous cell carcinoma) clinical c­onditions [5,6].            Facial pigmented lesions are often equivocal for the par-
The most stringent authors define a melanoma truly                 ticular skin anatomic architecture of the face as a result of



2                                                                      Original Article | Dermatol Pract Concept. 2023;13(2):e2023080
the absence of the rete ridges, the importance of adnexal          January 2017 and April 2021. Before excisional biopsy, all
structures and the varying degrees of sun-damaged epider-          lesions were recorded by means of digital dermoscopy at the
midis and solar elastosis in the dermis [10]. They commonly        department of Dermatology, University of Modena and Reg-
show a pseudo-network pattern bordering the unpigmented            gio Emilia. Only lesions with a diagnosis of melanoma and
hair follicle openings [10].                                       a high quality of dermoscopic images were included in this
    Acral lentiginous melanoma is another type of melanoma         study. After clinical and dermoscopic evaluation of 7-point
whose diagnosis is still challenging. Its predilection for acral   checklist score, single dermoscopic and histological features
sites determinates a delayed diagnosis at later stages asso-       were considered for lesions with a score of 2 or lower and a
ciated to a worse prognosis. An association between me-            diagnosis of melanoma (corresponding to dermoscopic fea-
chanical stress and acral melanoma has been proposed, but          tureless melanoma).
further investigations are necessary about it [11].                   The study was conducted according to the criteria set by
                                                                   the declaration of Helsinki.
Featureless Melanoma
ABCDE rule (Asymmetry, Border, Color, Diameter, Evolving)          Instruments
only provides 64% accuracy, indicating a necessity to have         For each lesion a complete set of clinical and dermoscopic
alternative diagnostic tools. The 7-point checklist score pro-     images, including the whole lesion, along with histopathol-
vides a useful algorithm for dermoscopy.                           ogy were available. Dermoscopic images were carried out by
    In 1998 Argenziano et al introduced a new ELM 7-point          means of Dermlite Photo (3GEN®) equipped with a Canon
checklist [12]. They identified seven standard ELM criteria,       G12 Camera.
selected by their prevalence in melanoma cases and their
histopathological correlates. According to odds ratios calcu-      Dermoscopic Criteria
lated, a score of 2 was given to 3 criteria (odd ratio more        The 7-point checklist score was calculated for each lesion as
than 5) defined as “major” criteria, and a score of 1 was          well as the frequencies of each different dermoscopic find-
allowed to the remaining 4 criteria (odd ratio lower than 5)       ing accounting for the score. Subsequently, melanomas with
called “minor” criteria. A minimum total score of 3 was nec-       a total score of 2 or lower, according the 7-point checklist
essary for diagnosis of melanoma [12,13].                          score, were classified as “featureless melanoma”.
    This new diagnostic algorithm revealed a sensitivity
of 97% (percentage of dermoscopic images of melanoma               Histopathological Analysis
scored as melanomas), a specificity of 71% (percentage of          The histopathological analysis was performed by a
dermoscopic images of naevi scored as benign naevi) with a         Board-Certified Pathologist (AMC).
diagnostic accuracy for melanoma of 68%, greater parame-
ters compared to the ABCDE rule [12].                              Statistics
    To increase sensitivity, a 7-point checklist revisited with
                                                                   Frequencies for each dermoscopic parameters were c­ alculated
a lower threshold for surgical excision has been proposed in
                                                                   in melanomas for each 7-point checklist score.
2011 by Argenziano et al [14]. One point was attributed to
each dermoscopic feature (without differentiation between
major criteria and minor ones) and the presence of only one        Results
finding was sufficient to propose removal. The necessity
to introduce an additional diagnostic tool arises from new         A total of 691 melanomas fulfilled inclusion criteria and
knowledges about dermoscopy [14].                                  were retrieved from the database. The 7-point checklist
                                                                   evaluation identified 19 “negative-featureless” melanomas
                                                                   scored between 0 and 2, 194 lesions scored between 3 and 4
Objectives
                                                                   and 478 lesions scored between 5 and 10 (Table 1).
The aim of the study was to improve the identification of             In the population with score ranging from 0 to 2, 8t mel-
featureless melanoma (scoring 0-2 according to the 7-point-­       anomas were not showing any positive dermoscopic clue
checklist) describing the variegated dermoscopic features and      (Figure 1 and 2), 3 presented a score 1, and 8 with total
their histopathological correlation.                               score 2 (6 presented one major feature positive and 2 having
                                                                   a positivity in two minor ones).

Methods                                                               Concerning the subgroup with a score of 3-4, 25 were
                                                                   associated with score 3 (23 presented 1 major feature with
Study samples included all melanomas excised based on              a minor one, and in only 2 cases we found a positivity in
clinical and/or dermoscopic findings in the period between         3 minor criteria), while 169 had a score of 4.



Original Article | Dermatol Pract Concept. 2023;13(2):e2023080                                                                3
        Frequencies of the dermoscopic features in lesions with          the atypical network (75%), followed by irregular dots and
the 7-point checklist ranging 0-2 and score 3 are reported in            globules (25%).
Table 2 and Table 3, respectively.                                           Concerning the population with 7-point checklist score
        In the population with a score of 1, the only positive           3, the most representative features were irregular dots and
criterion was irregular dots and globules (100%). Concern-               globules (84%) and atypical network (72%), followed by
ing the population scoring 2, the most frequent feature was              irregular diffuse pigmentation (16%), regression pattern
                                                                         (12%) and blue-whitish veil (12%).
    Table 1. Distribution of the study population                            In this work we present 19 difficult-to-diagnose-­melanomas
      according to the 7-point checklist score.                          in which the only dermoscopic evaluation could not play a

    7-Point checklist score            MM            % of MM             diagnostic role. Invaluable aids to improve sensibility and
                                                                         specificity for melanoma are represented by anamnesis, the
    0                                     8             1.2%
                                                                         ugly duckling sign, the signature naevus concept and clini-
    1                                     3            0.04%
                                                                         cal-dermoscopic follow-up. In this context, the aim of this
    2                                     8             1.2%
                                                                         study was to identify the most frequent dermoscopic and
    3                                    25             3.8%
                                                                         histopathological features of “featureless melanoma” trying
    4                                  169             24.3%
                                                                         to establish additional findings, too. All tumors, except for
    5                                  119             17.2%             a case with score 0 (superficial spreading melanoma with a
    6                                  193              28%              0.34 mm Breslow thickness), were in situ melanomas.
    7                                    76             11%                  In the population scoring 1, the 100% of the lesions
    8                                    39             5.6%             showed a globular pattern. In a published previous work, as
    9                                    33             4.8%             in our study, this pattern was found to be the rarest dermo-
 10                                      18             2.6%             scopic subtype of in situ melanoma (0.04% in the current
 TOT                                   691             100%              case series versus 2.6% in the previous one) and never aris-
                                                                         ing on a naevus [15].
MM = malignant melanoma.




Figure 1. Facial featureless melanoma scoring 0 of a patient sun-damaged skin affecting by rosacea. Any melanoma findings are recognizable
by dermoscopy. The HMB-45 staining, in the lower part of the right side, identify dermal and hypodermal tumoral nests.




Figure 2. Featureless melanoma with score of 0 showing a regular pigmented pattern. In the right side of the picture, it is possible to see the
histopathological image with irregular melanocytic nests along the rete ridges.



4                                                                             Original Article | Dermatol Pract Concept. 2023;13(2):e2023080
         Table 2. Frequencies of dermoscopic features in lesions with 7-point checklist score 0-2.
                Dermoscopic features                              Score 0                 Score 1                   Score 2
 Atypical network                                                    -                        -                    6 (75%)
 Blue-whitish veil                                                   -                        -                        -
 Atypical vessels                                                    -                        -                        -
 Irregular diffuse pigmentation (blotches)                           -                        -                   1 (12.5%)
 Peripheral streaks and/or pseudopods                                -                        -                        -
 Irregular dots and globules                                         -                   3 (100%)                  2 (25%)
 Regression pattern                                                  -                        -                   1 (12.5%)
 TOT                                                                8                         3                        8


Table 3. Frequencies of dermoscopic features in                      as peculiar dermoscopic characteristic, crystalline or chrysalis
     lesions with 7-point checklist score 3.                         structures. The presence of these findings is highly indicative
                                                                     of invasive melanoma (ticker than those without them) and
           Dermoscopic features                      Score 3
                                                                     cutaneous melanoma metastases [18].
 Atypical network                                   18 (72%)
 Blue-whitish veil                                   3 (12%)
 Atypical vessels                                     2 (8%)         Conclusions
 Irregular diffuse pigmentation (blotches)           4 (16%)
                                                                     Despite most research about dermoscopy has been managed
 Peripheral streaks and/or pseudopods                 1 (4%)
                                                                     in white skinned populations and few evidence about an
 Irregular dots and globules                        21 (84%)
                                                                     equal ability to work well in non-white populations, dermos-
 Regression pattern                                  3 (12%)
                                                                     copy is still the best diagnostic method for melanoma.
 TOT                                                    25               The 7-point checklist provides a simplification of stan-
                                                                     dard pattern analysis because of the algorithm based on a
    About melanomas with score 2, three-quarters of the              scoring system and the lower number of features to recognize.
cases presented a reticular pattern, in the remaining two            Compared with the latter, the specificity of the 7-point check-
lesions we noticed a globular patterns with additional re-           list method is worse (75% versus 90%) for its propensity
gression areas and irregular blotches, respectively. This last       to overclassify atypical melanocytic lesions as melanoma. On
was an in situ melanoma arising on a compound nevocytic              the other hand, its sensibility is greater (95%), particularly
naevus, showing, as additional feature, an inverse network.          for the early forms of cutaneous melanomas. This algorithm
Prominent skin marks (linear hypopigmented furrows with              can be learned more easily by nonexpert dermatologists.
an intersecting pattern) were found in other two cases. Ac-              In the daily practice it is more comfortable for many cli-
cording to several authors, the last dermoscopic finding is a        nicians to keep in mind a list of principles that trigger exci-
helpful indicator to differentiate an early or an in situ mela-      sion. In 2012, Lallas et al, edited several management rules
noma, especially on sun-damages skin, from a benign naevus           to recognize some difficult melanomas using an integrating
[16]. Supplementary features were considered. In one lesion          approach between clinical, dermoscopic, and histological
we noticed angulated lines (gray-brown not intersecting lines        examinations [21]). They summarized in seven simple and
that meet at angles larger than 90 degrees and can form po-          practical rules: 1) Look basically at all lesions, 2) Undress
lygonal shapes, rhomboids and zigzag pattern [17].                   high-risk patients (patients with a personal or family history
    In the subgroup with 0 points, one lesion, not presenting        of melanoma or other skin cancers, people under 50 years
neither classic nor additional features, was arose on a benign       presenting more than twenty naevi on the arms, patients
melanocytic naevus. Two melanomas showed as unique find-             over the age of 50 years with a chronic solar damage), 3) Use
ing the inverse network, one of which having the prominence          the “10 second rule” in single lesions (an approximated pe-
skin marks, too.                                                     riod to reach a conclusion in doubtful lesions), 4) Compare
    Borderline positive melanomas scoring 3 manifested mostly        and monitor multiple moles (considering that each patient
irregular dots and globules, followed by atypical network.           has a naevi’s individual phenotype, this principle results very
Supplementary features were considered. In two of twenty-five        useful in cases of atypical mole syndrome where the previous
lesions the prominent skin marks were noticed, angulated lines       rule could be ineffective), 5) Excise doubtful nodular lesions
in one case, and another one presenting both findings. In this       (especially for nodules positive to blue-black rule, milky-red
group we have a case of melanoma, arisen on a compound be-           areas and/or polymorphous vascular pattern), 6) Combine
nign naevus and with a Breslow thickness 0.3mm, exhibiting,          clinical and dermoscopic criteria, 7) Combine clinical and



Original Article | Dermatol Pract Concept. 2023;13(2):e2023080                                                                     5
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                                                                             HP. Confocal features of equivocal facial lesions on ­  severely
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