10.5826/dpc.1301a55
text/xml
2160-9381
2571
en
Giovanni Pellacani
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
early detection
Combined Use of Dermoscopy, Reflectance Confocal Microscopy, and Ex-Vivo Gene Expression Profiling to Detect a Micromelanoma Less Than 1 mm in Diameter
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2023-01-31
2022-05-02
2023-01-31
2023-03-01
e2023055
Dermatol Pract Concept
Giovanni Pellacani
2023/01/31
10.5826/dpc.1301a55
e2023055
Department of Dermatology, La Sapienza University, Rome, Italy
2160-9381
early detection
en
e2023055
Elmore JG, Barnhill RL, Elder DE, et al. Pathologists' diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study. BMJ. 2017;357:j2813. DOI: 10.1136/bmj.j2813. PMID: 28659278; PMCID: PMC5485913.
Combined Use of Dermoscopy, Reflectance Confocal Microscopy, and Ex-Vivo Gene Expression Profiling to Detect a Micromelanoma Less Than 1 mm in Diameter
https://dpcj.org/index.php/dpc/article/download/2571/1973
     Combined Use of Dermoscopy, Reflectance
 Confocal Microscopy and Ex-Vivo Gene Expression
  Profiling to Detect a Micro-Melanoma Less Than
                  1 mm in Diameter
   Alexander Witkowski1, Joanna Ludzik1,2, Jina Chung2, Claudia Lee2,3, Sancy Leachman2,
                                  Giovanni Pellacani4


1 Department of Dermatology, Oregon Health and Sciences University, Portland, Oregon
2 Department of Telemedicine and Bioinformatics, Jagiellonian University Medical College, Krakow, Poland
3 School of Medicine, University of California Riverside, Riverside, California
4 Department of Dermatology, La Sapienza University, Rome, Italy



Key words: reflectance confocal microscopy, dermoscopy, gene expression profiling, micro-melanoma, melanoma, skin cancer,
early detection
Citation: Witkowski AM, Ludzik J, Chung J, Lee C, Leachman S, Pellacani G. Combined use of dermoscopy, reflectance confocal
microscopy and ex-vivo gene expression profiling to detect a micro-melanoma less than 1 mm in diameter. Dermatol Pract Concept.
2023;13(1):e2023055. DOI: https://doi.org/10.5826/dpc.1301a55
Accepted: June 3, 2022; Published: January 2023
Copyright: ©2023 Witkowski 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: Claudia Lee, Department of Dermatology, Oregon Health and Sciences University, United States. E-mail: leecla@
ohsu.edu




Introduction                                                             Case Presentation
Micro-melanomas, or melanomas < 2 mm in diameter, are                    A 61-year-old female with no prior history of skin c­ancer
increasingly reported making screening methods like the                  presented for a skin examination. Clinical examination of
ABCD(E) acronym outdated. Early detection of melanoma                    her right cheek revealed a tiny, hyperpigmented dot not
remains the utmost important prognostic factor, therefore                previously noticed by the patient. Dermoscopy showed
understanding how to utilize different diagnostic tools is               sun-damaged skin with a dark brown macule and asymmet-
necessary to optimize detection of melanoma at its earli-                ric perifollicular hyperpigmentation. Reflectance confocal
est, most treatable stage. Using a combination of imaging                microscopy (RCM) revealed dendritic cells concentrated
and molecular techniques, we detected and confirmed a                    around a single hair follicle, consistent with folliculot-
micro-melanoma in situ measuring 0.65 mm in diameter.                    ropism (Figure 1). The final diameter incorporated the




Research Letter | Dermatol Pract Concept. 2023;13(1):e2023055                                                                         1
Figure 1. (A) Clinical image of pigmented skin lesion (arrow). (B) Zoomed digital dermoscopy image of the pigmented skin lesion present-
ing with folliculotropism (circle). Sites of control punch biopsies in areas of increased pigmentation (triangles). (C) Reflectance confocal
microscopy image (0.75 mm x 0.75 mm, measuring line bottom right corner: 0.25 mm) with presence of folliculotropism of pleomorphic
melanocytes. Melanoma in-situ maximal diameter measured: 0.65 mm.




Figure 2. Histopathology of the smallest reported melanoma. (A, B) H&E staining (A: 5X and B: 20X) showed an increased density of mostly
solitary melanocytes at the dermal-epidermal junction. (C, D) SOX10 immunostaining (C: 5X and D: 20X) showed a continuous proliferation
of melanocytes at the dermal-epidermal junction, consistent with melanoma in-situ.



farthest-reaching dendritic cell projections measuring at               Melan-A and SOX10 revealing irregular and heterogenous
0.65 mm. Initial histopathology showed a solar lentigo with-            melanocytic nests and single melanocytosis, consistent with
out atypia. Due to discordance with clinical-dermoscopic                melanoma in situ (MIS) ­(Figure 2). Additionally, the sample
concern, deeper sections were requested and stained with                underwent a diagnostic 23-gene expression profile (GEP)



2                                                                           Research Letter | Dermatol Pract Concept. 2023;13(1):e2023055
test which returned a positive result (suggestive of malig-         and RCM findings, initial histopathology reports were
nancy). National Comprehensive Cancer Network (NCCN)                benign. R
                                                                            ­ ecognizing histopathology has limitations due
guidelines make note of multiple ancillary diagnostic tests,        to sampling bias, potentially missing up to 10% of mel-
which includes diagnostic GEP, that can help to differentiate       anomas [5], we requested additional staining and 23-GEP
equivocal melanocytic lesions and may be useful in cases of         testing that ultimately revealed a diagnosis of MIS with a
clinical discordance [1]. In the context of these ancillary find-   diameter of 0.65 mm. This case attests to the heightened
ings final diagnosis of MIS was achieved. For control, four         diagnostic capabilities of multiple imaging and molecular
5x5 mm RCM image sets of the epidermis, dermal-­epidermal           tools when used in conjunction to confirm an early mela-
junction and upper dermis and two 2-mm punch biopsies               noma, which may result in better cosmetic, financial and
were completed adjacent to the biopsy site in the most pig-         patient morbidity.
mented areas and no atypical features were found confirm-
ing the absence of residual tumor in nearby locations.              References
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With the widespread adoption of dermoscopy, increasing                 DOI:10.1016/j.jaad.2020.03.122. PMID: 32360759.
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ing on dermoscopy alone, the smallest melanoma recorded                Diameter. Dermatol Pract Concept. 2021;11(2):e2021027. DOI:
measured at 1.3 mm [2] and another case enhanced by                    10.5826/dpc.1102a27. PMID: 33747632. PMCID: PMC7943215.
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amination tool that combined with digital follow-up fa-                28857145.
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that such small lesions cannot be malignant and investing              features and screening strategies for the detection of small-diameter
in its detection is wasteful, however Regio Pereira et al              melanomas. Clin Exp Dermatol. 2022;47(5):932-941. DOI:
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evaluated 86 melanomas <5 mm in diameter which found
                                                                    5. Elmore JG, Barnhill RL, Elder DE, et al. Pathologists’ diagnosis
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                                                                       of invasive melanoma and melanocytic proliferations: observer
tance of investigating suspicious lesions regardless of size.          accuracy and reproducibility study. BMJ. 2017;357:j2813. DOI:
­Although our case demonstrated suspicious dermoscopy                  10.1136/bmj.j2813. PMID: 28659278; PMCID: PMC5485913.




Research Letter | Dermatol Pract Concept. 2023;13(1):e2023055                                                                             3
