10.5826/dpc.1302a122
Introduction: Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic features at early stages, being difficult to differentiate from junctional nevi.
Objectives: This case series aims to raise awareness on the topic of misdiagnosis of early lentigo maligna as junctional nevi.
Methods: From the databases of three pigmented lesion clinics in Italy, Australia, and France, we retrieved all cases of lesions of the head/neck area with an initial histopathologic diagnosis of junctional nevus (JN) or dysplastic junctional nevus (DJN) which subsequently recurred and were ultimately diagnosed as melanoma. Moreover, we also retrieved those cases with an initial diagnosis of JN/DJN made on a partial biopsy that were diagnosed as melanoma after complete surgical removal.
Results: Here we report 14 cases in which the initial histologic diagnosis was junctional nevus or dysplastic junctional nevus. The lesions recurred over time with a final diagnosis of lentigo maligna.
Conclusions: Clinicians should critically question a given histologic diagnosis of junctional or dysplastic junctional nevus on the head/neck area if the clinical or dermoscopic features are discordant. Clinico-pathologic correlation is the best way to increase diagnostic accuracy and optimize management for the patient.
text/xml
2160-9381
2795
en
Giuseppe Argenziano
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
facial lesions
Junctional Nevus and Early Melanoma on Sun-Damaged Skin of the Head/Neck: A Clinico-Pathologic Challenge
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-04-29
2022-08-30
2023-04-29
2023-06-05
e2023122
Dermatol Pract Concept
Introduction: Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic features at early stages, being difficult to differentiate from junctional nevi.
Objectives: This case series aims to raise awareness on the topic of misdiagnosis of early lentigo maligna as junctional nevi.
Methods: From the databases of three pigmented lesion clinics in Italy, Australia, and France, we retrieved all cases of lesions of the head/neck area with an initial histopathologic diagnosis of junctional nevus (JN) or dysplastic junctional nevus (DJN) which subsequently recurred and were ultimately diagnosed as melanoma. Moreover, we also retrieved those cases with an initial diagnosis of JN/DJN made on a partial biopsy that were diagnosed as melanoma after complete surgical removal.
Results: Here we report 14 cases in which the initial histologic diagnosis was junctional nevus or dysplastic junctional nevus. The lesions recurred over time with a final diagnosis of lentigo maligna.
Conclusions: Clinicians should critically question a given histologic diagnosis of junctional or dysplastic junctional nevus on the head/neck area if the clinical or dermoscopic features are discordant. Clinico-pathologic correlation is the best way to increase diagnostic accuracy and optimize management for the patient.
Giuseppe Argenziano
2023/04/29
10.5826/dpc.1302a122
e2023122
Dermatology Unit, University of Campania L.Vanvitelli, Naples, Italy
2160-9381
facial lesions
en
e2023122
Grossman D, Okwundu N, Bartlett EK, et al. Prognostic Gene Expression Profiling in Cutaneous Melanoma: Identifying the Knowledge Gaps and Assessing the Clinical Benefit. JAMA Dermatol. 2020;156(9):1004-1011. DOI: 10.1001/jamadermatol.2020.1729. PMID: 32725204. PMCID: PMC8275355.
Junctional Nevus and Early Melanoma on Sun-Damaged Skin of the Head/Neck: A Clinico-Pathologic Challenge
https://dpcj.org/index.php/dpc/article/download/2795/2072
                Junctional Nevus and Early Melanoma
               on Sun-Damaged Skin of the Head/Neck:
                    a Clinico-Pathologic Challenge
            Elvira Moscarella1, Pascale Guitera2-4, Richard A. Scolyer2,3,5,6, Lilian Rocha5,
              Luc Thomas7,8,9, Andrea Ronchi10, Camila Scharf1, Gabriella Brancaccio1,
                                        Giuseppe Argenziano1


 1. Dermatology Unit, University of Campania L.Vanvitelli, Naples, Italy
 2. Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
 3. Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
 4. Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
 5. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, NSW, Australia
 6. Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
 7. Centre Hospitalier Lyon Sud, Lyons, France
 8. Lyon 1 University, Lyons, France
 9. Lyons cancer research center, Lyons, France
10. Pathology Unit, University of Campania L.Vanvitelli, Naples, Italy



Key words: melanoma, junctional nevus, dermoscopy, partial biopsy, facial lesions
Citation: Moscarella E, Guitera P, Scolyer RA, et al. Junctional Nevus and Early Melanoma on Sun-Damaged Skin of the Head/Neck:
A Clinico-Pathologic Challenge. Dermatol Pract Concept. 2023;13(2):e2023122. DOI: https://doi.org/10.5826/dpc.1302a122
Accepted: November 18, 2022; Published: April 2023
Copyright: ©2023 Moscarella 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: This work was supported by a National Health and Medical Research Council of Australia (NHMRC) Program Grant
(APP1093017) (to RAS). RAS is supported by an NHMRC Practitioner Fellowship (APP1141295). Support from colleagues at the authors’
respective institutions is also gratefully acknowledged.
Competing interests: RAS has received fees for professional services from F. Hoffmann-La Roche Ltd, Evaxion, Provectus
Biopharmaceuticals Australia, Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, AMGEN Inc., Bristol-Myers Squibb, Myriad
Genetics, GlaxoSmithKline.PG received Honoria form Metaoptima.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Elvira Moscarella, MD, Dermatology Unit, University of Campania L. Vanvitelli, Naples, Italy.
Email: Elvira.moscarella@gmail.com




  ABSTRACT             Introduction: Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic
                       features at early stages, being difficult to differentiate from junctional nevi.
                       Objectives: This case series aims to raise awareness on the topic of misdiagnosis of early lentigo
                       ­maligna as junctional nevi.
                       Methods: From the databases of three pigmented lesion clinics in Italy, Australia, and France,
                       we ­retrieved all cases of lesions of the head/neck area with an initial histopathologic diagnosis



Original Article | Dermatol Pract Concept. 2023;13(2):e2023122                                                                       1
                      of ­junctional nevus (JN) or dysplastic junctional nevus (DJN) which subsequently recurred and were
                      ultimately diagnosed as melanoma. Moreover, we also retrieved those cases with an initial diagnosis of
                      JN/DJN made on a partial biopsy that were diagnosed as melanoma after complete surgical removal.
                      Results: Here we report 14 cases in which the initial histologic diagnosis was junctional nevus or
                      dysplastic junctional nevus. The lesions recurred over time with a final diagnosis of lentigo maligna.
                      Conclusions: Clinicians should critically question a given histologic diagnosis of junctional or dys-
                      plastic junctional nevus on the head/neck area if the clinical or dermoscopic features are discordant.
                      Clinico-pathologic correlation is the best way to increase diagnostic accuracy and optimize manage-
                      ment for the patient.




Introduction                                                      Objectives
The clinical and histologic diagnosis of early melanoma on        With the aim of raising awareness on this clinico-pathologic
sun-damaged skin of the head/neck area may be challenging.        challenge, we present a series of 14 cases all of which were
Lentigo maligna (LM) is the commonest melanoma subtype            initially diagnosed as atypical/dysplastic junctional nevi but
occurring on the head and neck region. Clinically, LM usu-        were ultimately considered to represent melanoma. These in-
ally presents as a macule or patch of variable dimension and      clude two main scenarios, namely the difficulty of diagnosing
coloration, ill-defined borders and slowly grows over time        melanoma on a partial biopsy of suspicious lesions on the
[1-3]. Dermoscopically, atypical pseudo network with asym-        head/neck area, and the diagnosis of melanoma only after sev-
metric perifollicular pigmentation, peppering and/or gray         eral recurrences of completely excised flat junctional lesions.
circles are found in classical cases.
    LM is typically characterized histologically by a lentig-
                                                                  Methods
inous and sometimes nested proliferation of atypical mela-
nocytes arising in skin typified by sun damaged features of       From the databases of three pigmented lesion clinics in Italy,
epidermal atrophy and solar elastosis.                            Australia, and France, we retrieved all cases of lesions of the
    Cases of LM lacking the typical clinical and histologic       head/neck area with an initial histopathologic diagnosis of
hallmarks can be challenging to diagnose.                         junctional nevus (JN) or dysplastic junctional nevus (DJN)
    From a clinical and dermoscopic point of view, the main       which subsequently recurred and were ultimately diagnosed
differential diagnoses of LM include non-melanocytic be-          as melanoma. Moreover, we also retrieved those cases with an
nign lesions, such as solar lentigo, pigmented actinic kerato-    initial diagnosis of JN/DJN made on a partial biopsy that were
ses and lichen planus-like keratoses (LPLK). Nevi are rarely      diagnosed as melanoma after a complete surgical removal.
included in the differential diagnosis of LM, since most nevi        Information about patient demographic, lesion location,
on the head/neck of adults and elderly are of the compound        type of biopsy, and first and subsequent histopathologic
and dermal subtype. These nevi clinically present as dome         diagnoses were recorded. In most cases, the initial biopsies
shaped to nodular lesions, skin colored or only slightly pig-     were taken outside, and then the patient was referred to
mented [4].                                                       one of our specialized centers only after the lesion recurred.
    In recent years, it has become increasingly recognized        Given the difficulty to retrieve the material from the initial
that LM can include a prominent nested component mim-             biopsies, central histologic review was not performed.
icking a junctional or dysplastic nevus. Zalaudek et al first        All cases had clinical and dermoscopic images taken be-
reported one case of a lesion initially diagnosed as junctional   fore the final excision that led to the diagnosis of melanoma.
nevus on the neck of an adult patient that recurred twice         Dermoscopic evaluation was conducted by consensus by two
during a 4-year period, after apparent complete surgical          experienced dermoscopists (GB, CS). Follow up information
excision with clear margins, and was ultimately diagnosed         was recorded when available.
as LM [5]. Histopathologically, the diagnosis of LM can be           Ethic committee approval was not required, this was
challenging. In its early phases of development, LM may           analysis of datasets, where the data are properly anonymized.
display subtle features, with only mild cellular atypia and a
mixed junctional and lentiginous appearance of proliferating
                                                                  Results
melanocytes with occasional nests [6,7]. In this report, we
discuss the challenge of diagnosing facial atypical melano-       We collected 14 cases of pigmented lesions of the head and
cytic tumors with nested and lentiginous components.              neck with an initial diagnosis of JN/DJN that were ultimately

2                                                                     Original Article | Dermatol Pract Concept. 2023;13(2):e2023122
         Table 1. Demographic information of patients and history of lesions, including number
                               of recurrences and type of initial biopsy.
                                                             Type                                                         Years
             Age at                                       of biopsy           First           Total           Final        from
 Patient      first                     Lesion          (incisional=0;     histologic       number of      histologic      first
    Id      excision       Sex         location         excisional=1)      diagnosis       recurrences     diagnosis      biopsy
     1          45          M       Scalp                        1        DJN                   1         LM                 3
     2          71          M       Right temple                 1        DJN                   1         LM                 1
     3          48          F       Chin                         1        DJN                   1         LM                 2
     4          37          M       Left cheek                   1        JN                    4         LM                12
     5          60          F       Right eyelid                 1        DJN                   1         LM                 1
     6          51          F       Neck                         1        JN                    2         LM                 3
     7          53          F       Right cheek                  1        JN                    1         LMM                9
                                                                                                          0.5 mm
                                                                                                          Breslow
     8          45          M       Frontal                      1        JN                    1         LM                 1
     9          55          F       Right temple                 1        DJN                   1         LM                 3
    10          62          F       Right eyelid                 0        DJN                   2         LM                 7
    11          71          F       Left cheek                   0        DJN                   2         LM                 7
    12          53          M       Frontal                      0        DJN                    -        LM                 1
    13          89          F       Right cheek                  0        DJN                    -        LMM                -
                                                                                                          0.2 mm
                                                                                                          Breslow
    14          78          F       Scalp                        0        DJN                    -        LMM                -
                                                                                                          0.2 mm
                                                                                                          Breslow

DJN = dysplastic junctional nevus; JN = junctional nevus; LM = lentigo maligna; LMM = lentigo maligna melanoma.




considered melanoma. We can recognize two main scenar-               atypical pseudo network was identified in five cases (35.7%),
ios. Eleven cases had an initial diagnosis of JN/DJN and the         background erythema was seen in four lesions (28.6%), a
final diagnosis of melanoma was made only after several re-          regular pseudo-network was seen in three lesions (21.4%).
currences (cases 1 to 11 in Table 1). The majority of lesions re-    In two lesions, moth-eaten borders were observed (14.3%).
curred ones after a complete surgical excision (N = 7; 63.6 %),      Gray circles were seen in one lesion (7.1%). None of them
in 3 (27.3%) cases there were 2 recurrences over time, in 1 case     showed prevalent non-melanoma features [8].
the lesion initially diagnosed as JN recurred 4 times after com-
plete surgical excision, with a final diagnosis of LM 12 years
                                                                     Conclusions
after the first biopsy. Mean time from first biopsy to the latest
recurrence for the 11 cases was 4.5 years (range 1-12 years).        The diagnosis of early melanoma involving the head/neck
    The second scenario comprises three other cases in which         can be very difficult for both clinicians and pathologists. (9)
the diagnosis of DJN was made on partial biopsy; however,            Our series highlights this challenge that encompasses two
because of suspicious clinical and dermoscopic features the          main scenarios, namely, (i) the diagnostic underestimation
lesions were excised, and the final diagnosis on the whole           following a partial (incisional) biopsy, and (ii) the problem
specimen was LM (case 12, table 1) and early invasive mela-          of histopathologically inconspicuous features of very early
noma (cases 13-14, table 1). Clinical and demographic infor-         melanomas that were completely excised.
mation of the cases are summarized in Table 1, as well as data           Flat pigmented lesions of the head and neck are often
on the type of biopsy and the total number of recurrences.           large in diameter, or even if small in size, given their loca-
    All lesions were flat pigmented macules. Dermoscopically         tion, they are frequently biopsied with punch or partial
most lesions had ill-defined borders (84.6%). Structureless          shave biopsies to obtain a histologic diagnosis before per-
brown pigmentation was present in six lesions (42.9%),               forming larger excisions. In three cases in our series (cases
while a black pigmented blotch was seen in 2 (14.3%) le-             12-14, Table 1), the clinician decided to remove the lesion
sions. Gray globules were detected in six cases (42.9%). An          completely after an initial diagnosis of DJN was made on

Original Article | Dermatol Pract Concept. 2023;13(2):e2023122                                                                     3
     Figure 1. (A) A flat pigmented macule on the frontal region of a 53-year-old man. On an initial punch biopsy, the lesion was di-
     agnosed as atypical junctional nevus. The lesion was left untreated for 1 year. The patient sought consultation because the lesion
     was enlarging in size. (B) In dermoscopy, pseudo-network and asymmetrically pigmented follicular openings are seen. Histologic
     diagnosis after a complete surgical removal revealed a lentigo maligna (case #12 from Table 1).




           Figure 2. (A) A flat pigmented lesion on the frontal area in a 45-year-old man. The pigmented lesion was recurring one
           year after acomplete surgical excision, a scar is visible, the initial diagnosis was JN. (B) On dermoscopy brown pseudo
           network and gray circles were visible at the time of the recurrence. The lesion was excised with a final diagnosis of
           lentigo maligna (case #8 from Table 1).



partial biopsy. The lesions displayed features of melanoma              view, junctional nevi are extremely rare in the adult/elderly
at clinical and dermoscopic examination. In these 3 cases,              population, the majority facial naevi in the adult are intra-
the final histologic evaluation revealed LM and early inva-             dermal naevi of the Miescher type, clinically presenting as
sive melanomas of the LM subtype (LMM) (Figure 1). These                dome-shaped, hypopigmented or skin-colored nodules [10].
cases underline the need for clinicians to always critically            Clinicians should be aware of the possibility of diagnostic er-
evaluate a histologic diagnosis performed on partial biopsies           rors and should promote the best possible clinico-pathologic
in the clinical and dermoscopic context of the lesion. The              correlation for these cases. Of note, two of the partially bi-
final decision on patient management is in the hands of the             opsied lesions in our series were finally diagnosed as early
clinician, who should be aware of the possibility of a diag-            invasive melanomas, which would have progressed, even if
nostic underestimation on a small biopsy sample of the given            slowly, if left untreated.
lesion either due to non-representative sampling or simply                  In the other group (case 1 to 11, Table 1), we have a
insufficient tissue to enable full evaluation of the lesion [5-9].      series of lesions with an initial diagnosis of nevus that, de-
The histologic similarities between LM, LMM and DJN are                 spite displaying very subtle features histologically, behaved
well-known and can be difficult or impossible to distinguish            as melanoma, recurring and growing after apparently com-
on small biopsies and represent a recognized pitfall for pa-            plete surgical excision (Figure 2). The time to reach a definite
thologists [6,7]. Moreover, from an epidemiological point of            diagnosis ranged from 1 to 12 years after the initial biopsy,



4                                                                            Original Article | Dermatol Pract Concept. 2023;13(2):e2023122
  Figure 3. Histologic image of the case in figure 2. (A) Histology showing a lentiginous intraepidermal proliferation of melanocytes (right,
  blue arrowheads). A benign intradermal nevus is detectable on the left (yellow star) (H$E, original magnification 40x). (B) The melano-
  cytic proliferation is arranged in a continuous lentiginous pattern (H&E, original magnification 100x).



with a mean time of 4.5 years and a number of recurrences                 2. Ferrara G, Ligrone L, Zalaudek I, Mordente I, Argenziano
after complete excision ranging from 1 to 4.                                 G. L
                                                                                ­ entigo maligna in a young adult. Dermatology. 2008;
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6                                                                           Original Article | Dermatol Pract Concept. 2023;13(2):e2023122
