Clinical Characteristics and Special Considerations in the Management of Rare Melanoma Subtypes

Simple Summary Advancements in immune, targeted, and regional therapies have emerged in the past fifteen years in the management of high-risk, advanced, and metastatic melanomas. Rare melanoma variants include acral, mucosal, uveal, and desmoplastic melanoma. Though underrepresented in larger landmark trials for modern therapeutic options, results from these trials have been extrapolated and applied in the management of these rarer subtypes of melanoma. This article aims to review the current treatment recommendations for acral, mucosal, uveal, and desmoplastic melanomas. Abstract Rare histologic subtypes of melanoma, including acral, mucosal, uveal, and desmoplastic melanomas, only make up 5% of all diagnosed melanomas and are often underrepresented in large, randomized trials. Recent advancements in systemic therapy have shown marked improvement in pathologic response rates, improving progression-free and overall survival among cutaneous melanoma patients, but there are limited data to demonstrate improved survival among rarer subtypes of melanoma. Acral melanoma has a poor response to immunotherapy and is associated with worse survival. Mucosal melanoma has a large variability in its presentation, a poor prognosis, and a low mutational burden. Uveal melanoma is associated with a high rate of liver metastasis; recent adoption of infusion and perfusion therapies has demonstrated improved survival among these patients. Desmoplastic melanoma, a high-risk cutaneous melanoma, is associated with high locoregional recurrence rates and mutational burden, suggesting this melanoma may have enhanced response to immunotherapy. While these variants of melanoma represent distinct disease entities, this review highlights the clinicopathologic characteristics and treatment recommendations for each of these rare melanomas and highlights the utility of modern therapies for each of them.

• Publication year

  2024

• Venue

  Cancers

• Publication date

  2024-06-28

• Fields of study

  Medicine

• Identifiers
  DOI 10.3390/cancers16132395PMID 39001457PMCID 11240680
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A three-arm randomised phase II study of the MEK inhibitor selumetinib alone or in combination with paclitaxel in metastatic uveal melanoma.

  2024cited by this paper
• Cancer statistics, 2024

  2024influential reference
• Apatinib combined with camrelizumab in advanced acral melanoma patients: An open-label, single-arm phase 2 trial.

  2023influential reference
• Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

  2023cited by this paper
• Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma: The CAP 03 Phase 2 Nonrandomized Clinical Trial.

  2023influential reference
• Acral lentiginous melanoma incidence by sex, race, ethnicity, and stage in the United States, 2010-2019.

  2023influential reference
• Selective Internal Radiotherapy (SIRT) and Chemosaturation Percutaneous Hepatic Perfusion (CS-PHP) for Metastasized Uveal Melanoma: A Retrospective Comparative Study

  2023influential reference
• Isolated hyperthermic perfusions for cutaneous melanoma in-transit metastasis of the limb and uveal melanoma metastasis to the liver

  2023cited by this paper
• Cancer statistics, 2023

  2023cited by this paper
• Predictive Parameters in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan for Unresectable Liver Metastases from Uveal Melanoma: A Retrospective Pooled Analysis

  2022influential reference
• Neoadjuvant checkpoint inhibitor immunotherapy for resectable mucosal melanoma

  2022influential reference
• Efficacy comparison between anti-PD-1 antibody monotherapy and anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy for advanced acral melanoma: A retrospective, multicenter study of 254 Japanese patients.

  2022cited by this paper
• Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma

  2022cited by this paper
• Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study.

  2022cited by this paper
• Evolving Treatment Approaches to Mucosal Melanoma

  2022cited by this paper
• An Evidence-Based Staging System for Mucosal Melanoma: A Proposal

  2022cited by this paper
• Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study.

  2022cited by this paper
• Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis

  2022cited by this paper
• Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma

  2022cited by this paper
• Chemosaturation with percutaneous hepatic perfusion of melphalan for metastatic uveal melanoma

  2022cited by this paper
• Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma.

  2022influential reference
• Efficacy and tolerability of chemosaturation in patients with hepatic metastases from uveal melanoma

  2021influential reference
• A Mutational Survey of Acral Nevi.

  2021cited by this paper
• Acral Lentiginous Melanoma: A United States Multi-Center Substage Survival Analysis

  2021cited by this paper
• Caucasians with acral lentiginous melanoma have the same outcome as patients with stage- and limb-matched superficial spreading melanoma

  2021cited by this paper
• Desmoplastic melanoma: a review of its pathology and clinical behaviour, and of management recommendations in published guidelines

  2021cited by this paper
• The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma

  2021influential reference
• Percutaneous Hepatic Perfusion (PHP) with Melphalan in Liver-Dominant Metastatic Uveal Melanoma: The German Experience

  2021cited by this paper
• Selective internal radiation therapy for hepatic metastases of uveal melanoma: a systematic review.

  2021influential reference
• Combination of pembrolizumab plus temozolomide therapy in unresectable and advanced melanoma: a multicenter retrospective analysis in China

  2021influential reference
• Meta-Analysis of Isolated Hepatic Perfusion and Percutaneous Hepatic Perfusion as a Treatment for Uveal Melanoma Liver Metastases

  2021influential reference
• Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma.

  2021cited by this paper
• Sentinel Lymph Node Biopsy Positivity in Patients With Acral Lentiginous and Other Subtypes of Cutaneous Melanoma.

  2021influential reference
• Immune Checkpoint Inhibitors in Advanced Acral Melanoma: A Systematic Review

  2020cited by this paper
• Unresectable Hepatic Metastasis of Uveal Melanoma: Hepatic Chemosaturation with High-Dose Melphalan—Long-Term Overall Survival Negatively Correlates with Tumor Burden

  2020cited by this paper
• Percutaneous Hepatic Perfusion with Melphalan in Patients with Unresectable Ocular Melanoma Metastases Confined to the Liver: A Prospective Phase II Study

  2020influential reference
• The Mutational Landscape of Mucosal Melanoma.

  2020cited by this paper
• Anti-PD1 checkpoint inhibitor therapy in acral melanoma: A multicentre study of 193 Japanese patients.

  2020influential reference
• Desmoplastic Melanoma

  2020influential reference
• Complete response to talimogene laherparepvec in a primary acral lentiginous melanoma.

  2020cited by this paper
• Multicenter prospective phase II trial of nivolumab in patients with unresectable or metastatic mucosal melanoma

  2020cited by this paper
• The 2018 World Health Organization Classification of Cutaneous, Mucosal, and Uveal Melanoma: Detailed Analysis of 9 Distinct Subtypes Defined by Their Evolutionary Pathway.

  2020influential reference
• Epidemiological Study of Uveal Melanoma from US Surveillance, Epidemiology, and End Results Program (2010–2015)

  2020influential reference
• Survival after checkpoint inhibitors for metastatic acral, mucosal and uveal melanoma

  2020cited by this paper
• Molecular profiling of driver events in metastatic uveal melanoma

  2020cited by this paper
• Safety and efficacy of nivolumab in patients with rare melanoma subtypes who progressed on or after ipilimumab treatment: a single-arm, open-label, phase II study (CheckMate 172).

  2019influential reference
• Early Detection of Acral Melanoma: A Review of Clinical, Dermoscopic, Histopathologic, and Molecular Characteristics.

  2019cited by this paper
• Intra-arterial perfusion-based therapies for regionally metastatic cutaneous and uveal melanoma

  2019cited by this paper
• Targeted genomic profiling of acral melanoma.

  2019cited by this paper
• Melanoma on chronically sun-damaged skin: Lentigo maligna and desmoplastic melanoma.

  2019influential reference
• SELPAC: A 3 arm randomised phase II study of the MEK inhibitor selumetinib alone or in combination with paclitaxel (PT) in metastatic uveal melanoma (UM)

  2019cited by this paper
• Evaluation of the efficacy of immunotherapy for non-resectable mucosal melanoma

  2019cited by this paper
• Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets

  2019cited by this paper
• Desmoplastic melanoma: The role of pure and mixed subtype in sentinel lymph node biopsy and survival

  2019cited by this paper
• Chemosaturation with percutaneous hepatic perfusion of melphalan for liver-dominant metastatic uveal melanoma: a single center experience

  2019cited by this paper
• Re-biopsy of partially sampled thin melanoma impacts sentinel lymph node sampling as well as surgical margins

  2019influential reference
• Axitinib in Combination With Toripalimab, a Humanized Immunoglobulin G4 Monoclonal Antibody Against Programmed Cell Death-1, in Patients With Metastatic Mucosal Melanoma: An Open-Label Phase IB Trial

  2019influential reference
• A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151)

  2019influential reference
• Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT).

  2018cited by this paper
• Outcomes and Predictive Factors of Isolated Limb Infusion for Patients with In-transit Melanoma in China

  2018cited by this paper
• Survival Rates in Patients After Treatment for Metastasis From Uveal Melanoma

  2018cited by this paper
• Clinical and pathological features of acral melanoma in a South African population: A retrospective study.

  2018cited by this paper
• Desmoplastic melanoma

  2018cited by this paper
• Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma

  2018influential reference
• Multifactorial Analysis of Prognostic Factors and Survival Rates Among 706 Mucosal Melanoma Patients

  2018cited by this paper
• Selective internal radiation therapy (SIRT) as treatment for hepatic metastases of uveal melanoma: a Finnish nation-wide retrospective experience

  2018influential reference
• Whole-genome landscapes of major melanoma subtypes

  2017cited by this paper
• BRAF inhibitors: efficacious and tolerable in BRAF-mutant acral and mucosal melanoma.

  2017influential reference
• Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis.

  2017influential reference
• Uveal melanoma: relatively rare but deadly cancer

  2017influential reference
• The Utility of Sentinel Node Biopsy for Sinonasal Melanoma

  2017cited by this paper
• Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

  2017cited by this paper
• High response rate to PD-1 blockade in desmoplastic melanomas

  2017cited by this paper
• Percutaneous hepatic perfusion with melphalan in uveal melanoma: A safe and effective treatment modality in an orphan disease

  2017influential reference
• Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial.

  2016cited by this paper
• Combinatorial immunotherapy for melanoma

  2016cited by this paper
• The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma

  2016cited by this paper
• Tumor Characteristics, Genetics, Management, and the Risk of Metastasis in Uveal Melanoma

  2016cited by this paper
• Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis.

  2016cited by this paper
• Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases

  2016influential reference
• The efficacy of anti‐PD‐1 agents in acral and mucosal melanoma

  2016influential reference
• Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.

  2015cited by this paper
• Using risk factors for detection and prognostication of uveal melanoma

  2015influential reference
• Clinicopathologic Predictors of Survival in Patients with Desmoplastic Melanoma

  2015influential reference
• Effects of non‐amputative wide local excision on the local control and prognosis of in situ and invasive subungual melanoma

  2015cited by this paper
• Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.

  2015cited by this paper
• Isolated hepatic perfusion as a treatment for liver metastases of uveal melanoma.

  2015cited by this paper
• Analysis of recurrence patterns in acral versus nonacral melanoma: should histologic subtype influence treatment guidelines?

  2014cited by this paper
• Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial.

  2014cited by this paper
• Radiotherapy influences local control in patients with desmoplastic melanoma

  2014cited by this paper
• The mutational burden of acral melanoma revealed by whole‐genome sequencing and comparative analysis

  2014cited by this paper
• The role of adjuvant radiotherapy in the local management of desmoplastic melanoma

  2014cited by this paper
• Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin.

  2013cited by this paper
• Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma

  2013cited by this paper
• Socioeconomic status as a predictor of melanoma survival in a series of 1083 cases from Brazil: just a marker of health services accessibility?

  2013cited by this paper
• Desmoplastic Melanoma: Is There a Role for Sentinel Lymph Node Biopsy?

  2013cited by this paper
• Ipilimumab for patients with advanced mucosal melanoma.

  2013influential reference
• Mucosal Melanoma: Pathogenesis, Clinical Behavior, and Management

  2012influential reference
• Epidemiology and management of uveal melanoma.

  2012influential reference
• Mucosal melanoma: a clinically and biologically unique disease entity.

  2012influential reference

• The role of prognostic factors and inflammatory markers in identifying lymph node metastases of cutaneous malignant melanoma

  2026cites this paper
• Primary Melanoma of the Female Urethra: About One Case

  2025cites this paper
• Prognostic value of PRAME expression in uveal melanoma: a meta-analysis

  2025cites this paper
• The established of a machine learning model for predicting the efficacy of adjuvant interferon alpha1b in patients with advanced melanoma

  2024cites this paper