10.5826/dpc.1401a20
text/xml
2160-9381
3458
en
Juliano Peruzzo
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
pdl-1
Diffuse Melanosis Cutis in the Era of Targeted Therapy
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2024-01-31
2023-04-26
2024-01-31
2024-02-21
e2024020
Dermatol Pract Concept
Juliano Peruzzo
2024/01/31
10.5826/dpc.1401a20
e2024020
Department of Dermatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
2160-9381
pdl-1
en
e2024020
Sebaratnam DF, Martin LK, Venugopal SS, Mangos G, et al. Diffuse melanosis cutis in the setting of BRAF(V600E) metastatic melanoma. Int J Dermatol. 2014;53(11):1409–11.
Diffuse Melanosis Cutis in the Era of Targeted Therapy
https://dpcj.org/index.php/dpc/article/download/3458/2526
                        Diffuse Melanosis Cutis in the Era
                               of Targeted Therapy
         Fernanda Luiza Staub1, Bruna Ossanai Schoenardie1, Renan Rangel Bonamigo1,2,
                                       Juliano Peruzzo1


1 Department of Dermatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
2 Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil



Key words: melanoma, target therapy, hyperpigmentation, metastatic melanoma, pdl-1 inhibitors
Citation: Staub F, Ossanai Schoenardie, Rangel Bonamigo R, Peruzzo J. Diffuse Melanosis Cutis in the Era of Targeted Therapy. Dermatol
Pract Concept. 2024;14(1):e2024020. DOI: https://doi.org/10.5826/dpc.1401a20
Accepted: November 7, 2023; Published: January 2024
Copyright: ©2024 Staub 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: Juliano Peruzzo, Rua Ramiro Barcelos, 2350 - 90035-007 – Porto Alegre – RS, Brazil. Phone: +55 51 33598571
E-mail: julperuzzo@hcpa.edu.br




Introduction                                                                  Since the melanoma was positive for BRAF/V600E
                                                                         mutation with indeterminate PDL-1 expression, treatment
Metastatic melanoma can rarely present as a diffuse bluish-              with dabrafenib and trametinib had been instituted. She re-
gray discoloration of the skin, known as diffuse m
                                                 ­ elanosis              ported that the urine alterations resolved rapidly after ini-
cutis (DMC) [1,2]. As it can negatively influence quality of             tiating this treatment, but had little improvement in skin
life, therapeutic options for hyperpigmentation are crucial.             hyperpigmentation.
                                                                              As an attempt to attenuate the hyperpigmentation, we

Case Presentation                                                        prescribed 5% imiquimod for eight weeks, without any im-
                                                                         provement. We also attempted two sessions of Q-Switched
A 47-year-old woman was referred to the dermatology de-                  laser with no response after two sessions.
partment to investigate a diffuse hyperpigmentation of the
skin. She reported starting with progressive skin darkening
                                                                         Conclusions
5 months prior and having very dark urine 9 months prior
to her appointment. She had a diagnosis of cutaneous mel-                The exact physiopathology of DMC is still unclear [3]. It
anoma 6 years earlier and had discovered hepatic metas-                  is postulated that metastatic melanoma releases melanin
tasis 3 years after the melanoma diagnosis. Upon physical                ­precursors in the circulation (after cytolysis as a result of
examination, the patient presented with a diffuse blue-gray              rapid turnover of neoplastic deposits, central ischemia, im-
hyperpigmentation, which was more accentuated on the face                munological responses or oncologic therapies), which are
(Figure 1). Histopathology and Fontana–Masson stain of the               converted into melanin in the dermis and may be phagocy-
skin showed melanophages in a superficial perivascular lo-               tosed by native histiocytes, causing hyperpigmentation [2].
calization, compatible with dermic melanosis (Figure 2). The             Melanin precursors can also be excreted in urine causing
diagnosis of diffuse melanosis cutis (DMC) was established.              melanuria [2]. Other theories include the possibility that

Research Letter | Dermatol Pract Concept. 2024;14(1):e2024020                                                                        1
                     Figure 1. Diffuse blue-gray hyperpigmentation, more accentuated on the face.




       Figure 2. Histopathology (H&E and Fontana–Masson stains) showing melanin deposition in the superficial dermis with a
       perivascular distribution.


melanocyte proliferation might be stimulated by growth fac-         5 months [2]. It is a presentation of metastatic melanoma,
tors released by cancer cells or that DMC may be caused by          considered by some authors as a paraneoplastic condition,
dermal micrometastasis producing melanin [4]. F
                                              ­ urthermore,         that can assist in the diagnosis of advanced melanoma [4].
more than one pathway may contribute to the etiopatho-                  BRAF-MEK inhibitors have significantly expanded
genesis of DMC. Pigmentation is most frequently seen in a           life-expectancy in metastatic melanoma. Our patient died 24
photo-distributed pattern [5]. Histologic findings include in-      months after first developing DMC. Interestingly, as previ-
creased melanin in dermal histiocytes, free pigment between         ously reported, our patient melanuria completely resolved
collagen stroma and epidermal hyperpigmentation [2].                after initiating treatment with dabrafenib and trametinib,
Melanophages extending to subcutis and skeletal muscle can          although no improvement in skin hyperpigmentation was
also be seen [6].                                                   seen [1].
    There is no treatment for DMC. Successful treatment of              Even though our attempts to treat DMC were not suc-
localized melanosis cutis with imiquimod cream 5% has been          cessful, we believe this is a field which ought to be studied
described [5], although our patient did not present with the        further. The cosmetic impact of DMC on patients has not
same outcome. DMC is a bad prognosis marker, with a mean            been explored as it was associated with a very poor prog-
life expectancy after developing hyperpigmentation of 4 to          nosis. However, since the advent of targeted therapy and



2                                                                       Research Letter | Dermatol Pract Concept. 2024;14(1):e2024020
immunotherapy, these patients are living longer, so treat-              3. Piana S, Longo C. Diffuse Melanosis and Melanuria. N Engl J
ments for melanosis might improve their quality of life.                   Med. 2019;380(12):1166. DOI: 10.1056/NEJMicm1810151.
                                                                           PMID: 30893538.
                                                                        4. Chinai B, Piazza M, Patel R, Roy S. Diffuse melanosis cutis:
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Research Letter | Dermatol Pract Concept. 2024;14(1):e2024020                                                                               3
