Advance in Melanoma

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Dermatology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 22557

Special Issue Editors

Dermatology Clinic, University of Turin , Medical Sciences Department, Torino, Italy
Interests: melanoma; adjuvant therapy; immunotherapy; target therapy; skin lymphoma
Dermatology Clinic, University of Turin , Medical Sciences Department, Torino, Italy
Interests: melanoma; adjuvant therapy; immunotherapy; target therapy; skin lymphoma; dermoscopy
Dermatology Clinic, University of Turin , Medical Sciences Department, Torino, Italy
Interests: melanoma; sentinel lymph node; dermoscopy; genetics; genomics

Special Issue Information

Dear Colleagues,

As you know, melanoma represents the skin cancer characterized by the potentially most unfavorable clinical course. Based on the natural history of the disease and the associated risks of progression and metastasis, four crucial articulations associated with potential impact on patient prognosis can be identified:

1) Identification of patients at risk that need periodic close monitoring by identifying associations between genotypic and phenotypic features;

2) Identification of predictive parameters on the risk of recurrence, progression, and metastasis, including reinterpretation of classical prognostic factors such as sentinel node biopsy;

3) Identification of parameters associated with a lower risk of recurrence after stage III adjuvant therapy, both phenotypical and genomics;

4) Identification of parameters associated with treatment response (stage IV metastatic melanoma) and residual disease persistence.

This Special Issue will address the most recent and relevant scientific findings regarding advances in melanoma.

Prof. Maria Teresa Fierro
Dr. Pietro Quaglino
Dr. Simone Ribero
Guest Editors

Manuscript Submission Information

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Keywords

  • melanoma
  • adjuvant therapy
  • immunotherapy
  • target therapy
  • skin lymphoma
  • prognostic factors

Published Papers (8 papers)

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Research

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9 pages, 431 KiB  
Article
Sentinel Lymph Node Biopsy in Malignant Melanoma of the Head and Neck: A Single Center Experience
by Marco Rubatto, Franco Picciotto, Giovenale Moirano, Enrico Fruttero, Virginia Caliendo, Silvia Borriello, Nadia Sciamarrelli, Paolo Fava, Rebecca Senetta, Adriana Lesca, Anna Sapino, Désirée Deandreis, Simone Ribero and Pietro Quaglino
J. Clin. Med. 2023, 12(2), 553; https://doi.org/10.3390/jcm12020553 - 10 Jan 2023
Cited by 1 | Viewed by 1570
Abstract
Purpose: This study evaluated the characteristics of patients with head and neck (H&N) melanoma who underwent sentinel lymph node biopsy (SNLB) and assessed the clinical course of patients categorizing subjects according to SLNB status and melanoma location (scalp area vs. non-scalp areas). Methods: [...] Read more.
Purpose: This study evaluated the characteristics of patients with head and neck (H&N) melanoma who underwent sentinel lymph node biopsy (SNLB) and assessed the clinical course of patients categorizing subjects according to SLNB status and melanoma location (scalp area vs. non-scalp areas). Methods: Patients undergoing SLNB for melanoma of H&N from 2015 to 2021 were prospectively characterized according to sentinel lymph node (SLN) status. SPECT/CT had been previously performed. Patients were followed until the first adverse event to evaluate progression-free survival. Results: 93 patients were enrolled. SLNB was negative in 75 patients. The median Breslow index was higher for patients with positive SLNB compared with patients with negative SLNB. In addition, the Breslow index was higher for melanoma of the scalp compared with non-scalp melanoma. The median follow-up was 24.8 months. Progression occurred at the systemic level in the 62.5% of cases. There was a significant association between positive SLNB and progression (p-value < 0.01) of disease, with lower progression-free survival for patients with melanoma of the scalp compared with those with melanoma at other anatomic sites (p-value: 0.15). Conclusions: Scalp melanomas are more aggressive than other types of H&N melanomas. Sentinel lymph node status is the strongest prognostic criterion for recurrence. Full article
(This article belongs to the Special Issue Advance in Melanoma)
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10 pages, 3080 KiB  
Article
Risk Stratification and Clinical Characteristics of Patients with Late Recurrence of Melanoma (>10 Years)
by Robin Reschke, Konstantin Dumann and Mirjana Ziemer
J. Clin. Med. 2022, 11(7), 2026; https://doi.org/10.3390/jcm11072026 - 05 Apr 2022
Cited by 4 | Viewed by 1963
Abstract
Background: Most patients with high-risk melanomas develop metastasis within the first few years after diagnosis. However, late recurrence of melanoma is seen in patients that metastasize more than 10 years after the primary diagnosis; a metastasis after 15 years is considered an ultra-late [...] Read more.
Background: Most patients with high-risk melanomas develop metastasis within the first few years after diagnosis. However, late recurrence of melanoma is seen in patients that metastasize more than 10 years after the primary diagnosis; a metastasis after 15 years is considered an ultra-late recurrence. It is critical to better understand the clinical and biological characteristics of this subset of melanoma patients in order to offer an individual treatment plan and prevent metastasis. Methods: We retrospectively analyzed melanoma patients with recurrence ≥10 years after a primary diagnosis documented between 1993 and 2012 at the skin cancer center of the University Medical Center Leipzig, Germany. We conducted a comprehensive review of the literature and compared the results with our data. Available archived primary melanoma tissue was investigated with a seven-marker immunohistochemical signature (immunoprint®) previously validated to reliably identify high-risk patients within stages IB-III. Results: Out of 36 analyzed patients, a third metastasized ultra-late (≥15 years). The mean age at initial diagnosis was 51 years, with women being diagnosed comparatively younger than men. The largest proportion of patients with late recurrence had primary melanomas located on the trunk. The immunoprint® signature of the available primary melanomas allowed the accurate prediction of a high risk. However, it is difficult to draw a definitive conclusion from the small number of cases that could be analyzed with immunoprint® (n = 2) in this study. Apart from the primary tumor characteristics, the laboratory values at time of metastasis, comorbidities and outcome are also shown. Conclusion: Late and ultra-late recurrent melanomas seem not to differ from melanomas in general, apart from a distinctly higher proportion of lower leg localizations in ultra-late recurrent melanomas. The immunoprint® signature may help to identify high-risk primary tumors at the time of initial diagnosis. However, apart from the risk profile of the primary tumor, it seems that individual immune surveillance can control residual tumor cells for more than a decade. Advanced age and increasing comorbidities may contribute to a disturbed immunological balance. Full article
(This article belongs to the Special Issue Advance in Melanoma)
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14 pages, 2110 KiB  
Article
Multispectral Imaging Algorithm Predicts Breslow Thickness of Melanoma
by Szabolcs Bozsányi, Noémi Nóra Varga, Klára Farkas, András Bánvölgyi, Kende Lőrincz, Ilze Lihacova, Alexey Lihachev, Emilija Vija Plorina, Áron Bartha, Antal Jobbágy, Enikő Kuroli, György Paragh, Péter Holló, Márta Medvecz, Norbert Kiss and Norbert M. Wikonkál
J. Clin. Med. 2022, 11(1), 189; https://doi.org/10.3390/jcm11010189 - 30 Dec 2021
Cited by 4 | Viewed by 2949
Abstract
Breslow thickness is a major prognostic factor for melanoma. It is based on histopathological evaluation, and thus it is not available to aid clinical decision making at the time of the initial melanoma diagnosis. In this work, we assessed the efficacy of multispectral [...] Read more.
Breslow thickness is a major prognostic factor for melanoma. It is based on histopathological evaluation, and thus it is not available to aid clinical decision making at the time of the initial melanoma diagnosis. In this work, we assessed the efficacy of multispectral imaging (MSI) to predict Breslow thickness and developed a classification algorithm to determine optimal safety margins of the melanoma excision. First, we excluded nevi from the analysis with a novel quantitative parameter. Parameter s’ could differentiate nevi from melanomas with a sensitivity of 89.60% and specificity of 88.11%. Following this step, we have categorized melanomas into three different subgroups based on Breslow thickness (≤1 mm, 1–2 mm and >2 mm) with a sensitivity of 78.00% and specificity of 89.00% and a substantial agreement (κ = 0.67; 95% CI, 0.58–0.76). We compared our results to the performance of dermatologists and dermatology residents who assessed dermoscopic and clinical images of these melanomas, and reached a sensitivity of 60.38% and specificity of 80.86% with a moderate agreement (κ = 0.41; 95% CI, 0.39–0.43). Based on our findings, this novel method may help predict the appropriate safety margins for curative melanoma excision. Full article
(This article belongs to the Special Issue Advance in Melanoma)
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11 pages, 533 KiB  
Article
Proportion of Thick versus Thin Melanomas as a Benchmarking Tool
by Calogero Pagliarello, Serena Magi, Laura Mazzoni and Ignazio Stanganelli
J. Clin. Med. 2021, 10(23), 5545; https://doi.org/10.3390/jcm10235545 - 26 Nov 2021
Cited by 5 | Viewed by 1150
Abstract
Background: The ratio of benign moles excised for each malignant melanoma diagnosed (number-needed-to-excise (NNE)) is a metric used to express the efficiency of diagnostic accuracy of melanoma. The literature suggests a progressive effort to reduce the NNE, thus raising concerns about missing early [...] Read more.
Background: The ratio of benign moles excised for each malignant melanoma diagnosed (number-needed-to-excise (NNE)) is a metric used to express the efficiency of diagnostic accuracy of melanoma. The literature suggests a progressive effort to reduce the NNE, thus raising concerns about missing early melanoma because the NNE does not capture the most significant outcome for melanoma prognosis, which is linked to the Breslow thickness. A lower NNE could reduce health costs related to melanoma diagnosis only if doing so does not increase the proportion of thicker melanomas. Objectives: The diagnostic performance by two tertiary referral centres using the NNE and proportion of thick (Breslow thickness > 1 mm) versus thin (Breslow thickness ≤ 1 mm) excised melanoma (thick/thin ratio: TTR) was compared to determine if a lower NNE is associated with a greater proportion of thicker melanoma. Combining TTR with NNE allows a better estimate of the effectiveness in melanoma diagnosis, assessing both the overall cost for a given pool of excised melanomas and costs due to unnecessary nevi excision at a particular dermatology centre. Methods: Demographic data and Breslow thickness of excised melanoma were extracted from patient histologic records at two referral centres for melanoma (Parma Dermatology Unit and Ravenna and Meldola Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori. IRCCS (IRST)) on all skin tumours excised between 2002 and 2011 and diagnosed as melanoma or melanocytic nevus. NNE and TTR were calculated and compared among the considered variables. Logistic regression was used to assess the contribution of each variable in predicting a higher TTR. Results: Data from 16,738 excised lesions were analysed. The IRST Unit reported a mean NNE of 4.6, whereas the Parma Unit excised 10.6 nevi for each melanoma. No statistically significant differences existed in the mean (IRST Unit, 0.56 ± 0.89 mm; Parma Unit, 1.07 ± 2.2 mm) and median (range) Breslow thickness (IRST Unit, 0.4 (9) mm; Parma Unit 0.4 (30) mm). The TTR between centres was significantly different (Parma Unit, 24%; IRST Unit, 12%; p < 0.001). Based on logistic regression, the diagnosing centre was the most powerful factor in determining a thickness of >1 mm among diagnosed melanomas (OR = 1.8; 95% CI, 1.2–2.7; p < 0.01), with all other factors being equal. The NNE decreased at both centres from younger-to-older patients, whereas the TTR increased simultaneously; however, the increase in TTR was non-significantly related to NNE reduction after adjusting for confounders (age, gender, and localization). Conclusions: A better diagnostic performance is capable of reducing the NNE and TTR, i.e., unnecessary excisions of melanocytic nevi can be reduced without increasing the risk of overlooking melanomas. The TTR, in addition to the NNE, allows stakeholders to better estimate the effectiveness in melanoma diagnosis because both overall costs for a given pool of excised melanomas and costs due for unnecessary nevi excision at a particular dermatology centre can be compared. Full article
(This article belongs to the Special Issue Advance in Melanoma)
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20 pages, 16304 KiB  
Article
Clinical Significance of Tumor Microenvironment in Acral Melanoma: A Large Single-Institution Study of Caucasians
by Aneta Maria Borkowska, Anna Szumera-Ciećkiewicz, Maria Chraszczewska, Kamil Sokół, Tomasz Goryń and Piotr Łukasz Rutkowski
J. Clin. Med. 2021, 10(7), 1452; https://doi.org/10.3390/jcm10071452 - 01 Apr 2021
Cited by 4 | Viewed by 1907
Abstract
Background: The presence of tumor-infiltrating lymphocytes (TILs) in many studies is associated with a better prognosis in melanoma patients. Programmed death-ligand 1 (PD-L1) expression has a significant value in predicting several cancers, but its role in melanoma remains ambiguous. The study aims to [...] Read more.
Background: The presence of tumor-infiltrating lymphocytes (TILs) in many studies is associated with a better prognosis in melanoma patients. Programmed death-ligand 1 (PD-L1) expression has a significant value in predicting several cancers, but its role in melanoma remains ambiguous. The study aims to report a comprehensive analysis of TILs characteristics and their impact on survival in primary acral melanoma (AM). Methods: Clinical and pathological features and survival outcomes were investigated in 70 patients with AM. Immunohistochemical quantitative analysis of TILs, including expression of CD4, CD8, FOXP3, PD-1, and PD-L1, on melanoma cells was performed. Results: Kaplan-Meier analysis showed significant differences in overall survival (OS) for CD4+ (p = 0.021), CD8+ (p = 0.037), FOXP3+ (p = 0.007), and TILs density (p = 0.043). In univariate analysis of immunohistochemical features, FOXP3, CD4, CD8, PD-1, and Melanoma Institute of Australia (MIA) grading TILs (grade, density, and distribution) were correlated with survival. The higher density of FOXP3-positive cells was an independent factor associated with better survival. Conclusions: High TILs content (classed as brisk Clark scale and marked/diffuse TILs MIA grade) regardless of its immunophenotype was associated with better survival outcomes in AM. PD-L1 expression on tumor cells did not influence OS and was independent of clinical and pathological characteristics. We demonstrated that TILs are significant biomarkers in sentinel lymph node status prediction. Full article
(This article belongs to the Special Issue Advance in Melanoma)
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8 pages, 605 KiB  
Article
Preoperative Screening CT and PET/CT Scanning for Acral Melanoma: Is it Necessary?
by Taketoshi Ide, Takamichi Ito, Maiko Wada-Ohno and Masutaka Furue
J. Clin. Med. 2021, 10(4), 811; https://doi.org/10.3390/jcm10040811 - 17 Feb 2021
Cited by 2 | Viewed by 1733
Abstract
The efficacy of preoperative imaging for acral melanoma (AM) has not been fully evaluated. We examined the accuracy of imaging modalities in the detection of nodal and distant metastases in patients with AM. A retrospective review of 109 patients with AM was performed. [...] Read more.
The efficacy of preoperative imaging for acral melanoma (AM) has not been fully evaluated. We examined the accuracy of imaging modalities in the detection of nodal and distant metastases in patients with AM. A retrospective review of 109 patients with AM was performed. All patients had no clinical signs suggestive of distant metastases, and underwent preoperative screening computed tomography (CT) and positron emission tomography (PET)/CT scans. Of 100 patients without lymphadenopathy, 17 patients were suspected of having nodal metastasis in CT and PET/CT, but only two of them were confirmed on histopathological analysis. On the other hand, 12 out of 83 negatively imaged patients showed histopathological signs of nodal metastasis; thus, the sensitivity and specificity of nodal detection were 14.3% and 82.6%, respectively. Regard to the detection of distant metastases, four patients were suspected of having metastasis, but this was later ruled out. The remaining 96 negatively imaged patients were confirmed to have no metastasis at the time of CT and PET/CT by the follow-up. In contrast, distant metastases were found by CT and PET/CT in four of nine patients (44.4%) with lymphadenopathy. Routine preoperative CT and PET/CT for AM patients without lymphadenopathy may not be warranted because of low sensitivity and specificity, but it can be considered for those with lymphadenopathy. Full article
(This article belongs to the Special Issue Advance in Melanoma)
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Review

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11 pages, 1760 KiB  
Review
Oral Manifestations in Melanoma Patients Treated with Target or Immunomodulatory Therapies
by Emi Dika, Martina Lambertini, Bruna Gouveia, Martina Mussi, Emanuela Marcelli, Elena Campione, Carlotta Gurioli, Barbara Melotti, Aurora Alessandrini and Simone Ribero
J. Clin. Med. 2021, 10(6), 1283; https://doi.org/10.3390/jcm10061283 - 19 Mar 2021
Cited by 7 | Viewed by 2497
Abstract
Background: BRAF (v-raf murine sarcoma viral oncogene homolog B1) and MEK (mitogen activated protein kinase) inhibitors, as well as immunotherapy against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1), have shown good results in [...] Read more.
Background: BRAF (v-raf murine sarcoma viral oncogene homolog B1) and MEK (mitogen activated protein kinase) inhibitors, as well as immunotherapy against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1), have shown good results in improving the disease-free survival of patients with metastatic melanoma (MM). The aim of this review is to summarize the main oral adverse events (oAEs) occurring in patients undergoing target or immunotherapy. We proposed two separate sections: oAEs during the treatment with (1) target therapies with BRAF and MEK inhibitors and tyrosine kinase inhibitors (gingival hyperplasia, pigmentation disorders, squamo-proliferative lesions) and (2) immunotherapies with CTLA-4 or PD1 inhibitors (lichenoid reactions, immuno-bullous reactions, xerostomia and other reactions). Adverse events frequently include oAEs, although these are often misdiagnosed and under-reported. Indeed, the oral cavity is not routinely evaluated during clinical practice. The symptomatology related to oAEs is significant since it may represent the first manifestation of a severe systemic reaction, possibly leading to difficulties in nutrition with a consequent impact on patients’ quality of life. A careful examination of the oral cavity is recommended during the evaluation of oncologic patients in order to promptly detect the onset of new manifestations. Full article
(This article belongs to the Special Issue Advance in Melanoma)
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15 pages, 3629 KiB  
Review
Cutaneous and Mucosal Melanomas of Uncommon Sites: Where Do We Stand Now?
by Emi Dika, Martina Lambertini, Cristina Pellegrini, Giulia Veronesi, Barbara Melotti, Mattia Riefolo, Francesca Sperandi, Annalisa Patrizi, Costantino Ricci, Martina Mussi and Maria Concetta Fargnoli
J. Clin. Med. 2021, 10(3), 478; https://doi.org/10.3390/jcm10030478 - 28 Jan 2021
Cited by 12 | Viewed by 7281
Abstract
Melanomas arising at uncommon sites include a group of lesions related to unusual localizations in specific ethnic groups. The rarity of the disease often represents a limit to the participation of patients in specific trials. However, this peculiar genetic scenario has important therapeutic [...] Read more.
Melanomas arising at uncommon sites include a group of lesions related to unusual localizations in specific ethnic groups. The rarity of the disease often represents a limit to the participation of patients in specific trials. However, this peculiar genetic scenario has important therapeutic implications regarding new oncologic therapies. The aim of this article is to review the clinical features, somatic alterations and therapeutic options for melanomas of uncommon sites. They can be classified as cutaneous and mucosal lesions affecting the nail apparatus, palms/soles, oral mucosa, genital area and scalp. The prognosis may be worse compared to melanomas of other districts, and a prompt diagnosis may dramatically influence the outcome. Dermatologists and oncologists should therefore distinguish this melanoma subgroup in terms of surgical intervention and medical treatment. Due to the lack of mutations in genes usually found in cutaneous melanomas, the discovery of novel targets is required to develop new strategies and to change the prognosis of non-responders or wild-type patients. Full article
(This article belongs to the Special Issue Advance in Melanoma)
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