Acral lentiginous melanoma: Basic facts, biological characteristics and research perspectives of an understudied disease

Basurto-Lozada, Patricia; Molina-Aguilar, Christian; Castañeda-García, Carolina; Vázquez-Cruz, Martha Estefanía; Garcia-Salinas, Omar Isaac; Álvarez-Cano, Alethia; Martínez-Said, Héctor; Roldán–Marín, Rodrigo; Adams, David J.; Possik, Patrícia A.; Robles‐Espinoza, Carla Daniela

doi:10.1111/pcmr.12885

Cited by 84 publications

(110 citation statements)

References 104 publications

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“…AM is a rare subtype of malignant melanoma occurring in the non-hair-bearing skin of the palms, soles, and nail apparatus [1]. Despite a similar incidence among different ethnicities, AM is the commonest melanoma in Asian, African, and Hispanic people, given the low incidence of other cutaneous melanomas [1][2][3]14]. Most studies on AM were mainly conducted on these populations and European-derived people were often marginally included [15][16][17][18][19][20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

“…Patients with AM are typically diagnosed at an advanced stage of disease with thick and ulcerated primary tumor and a high likelihood of metastases [4][5][6][7][8]. The treatment is the same as for the other cutaneous melanomas: wide surgical removal of the primary tumor and, if feasible, of regional nodal metastases for local disease and immunotherapy or targeted therapy (more rarely chemotherapy) for metastatic disease [9] From the pathological point of view, AM is classified as acral lentiginous melanoma (ALM), which is the most common and aggressive form, superficial spreading melanoma (SSM), nodular melanoma (NM), and nevoid melanoma [9][10][11][12][13][14]. These differ not only in morphology but also in etiology, pathogenesis, and underlying molecular alterations [10].…”

Section: Introductionmentioning

confidence: 99%

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The Molecular Landscape of Primary Acral Melanoma: A Multicenter Study of the Italian Melanoma Intergroup (IMI)

Elefanti

Zamuner

Fiore

et al. 2021

IJMS

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Acral melanoma (AM) is a rare and aggressive subtype of melanoma affecting the palms, soles, and nail apparatus with similar incidence among different ethnicities. AM is unrelated to ultraviolet radiation and has a low mutation burden but frequent chromosomal rearrangements and gene amplifications. Next generation sequencing of 33 genes and somatic copy number variation (CNV) analysis with genome-wide single nucleotide polymorphism arrays were performed in order to molecularly characterize 48 primary AMs of Italian patients in association with clinicopathological and prognostic features. BRAF was the most commonly mutated gene, followed by NRAS and TP53, whereas TERT promoter, KIT, and ARID1A were less frequently mutated. Gains and losses were recurrently found in the 1q, 6p, 7, 8q, 20 and 22 chromosomes involving PREX2, RAC1, KMT2C, BRAF, CCND1, TERT, and AKT3 genes, and in the 6q, 9, 10, 11q and 16q chromosomes including CDKN2A, PTEN, and ADAMTS18 genes, respectively. This study confirmed the variety of gene mutations and the high load of CNV in primary AM. Some genomic alterations were associated with histologic prognostic features. BRAF mutations, found with a higher rate than previously reported, correlated with a low Breslow thickness, low mitotic count, low CNV of the AMs, and with early-stage of disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Molecular Landscape of Primary Acral Melanoma: A Multicenter Study of the Italian Melanoma Intergroup (IMI)

Elefanti

Zamuner

Fiore

et al. 2021

IJMS

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“…The understanding of the etiology of ALM is rudimentary, unclear, and contentious. It may be multifactorial, including interaction between genetic variants of small effect and certain environmental triggers, such as trauma [40]. Last but not least, we do not have any information about UV or sunlight exposure in our database.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Human Papillomavirus Infection on Skin Cancer: A Population-Based Cohort Study

et al. 2020

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Background This study investigated the correlation between a history of human papillomavirus (HPV) infection and skin cancer risk. Materials and Methods The study cohort comprised 26,919 patients with newly diagnosed HPV infection between 2000 and 2012; with the use of computer‐generated numbers, patients without previous HPV infection were randomly selected as the comparison cohort. The patients in the HPV infection cohort were matched to comparison individuals at a 1:4 ratio by demographic characteristics and comorbidities. All study individuals were followed up until they developed skin cancer, withdrew from the National Health Insurance program, were lost to follow‐up, or until the end of 2013. The primary outcome was subsequent skin cancer development. Cox proportional hazards regression analysis was used to analyze the risk of skin cancer with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. Results The adjusted HR of skin cancer for patients with HPV relative to controls was 2.45 after adjusting sex, age and comorbidities. (95% CI, 1.44–4.18, p < .01). The subgroup analysis indicated that a patient with HPV infection had a significantly greater risk of skin cancer if they were aged >40 years. Notably, a risk of skin cancer was found in the group diagnosed with HPV within the first 5 years after the index date (adjusted HR, 3.12; with 95% CI, 1.58–5.54). Sensitivity analysis by propensity score, matching with balanced sex, age, and comorbidities, showed consistent results. Conclusion A history of HPV infection is associated with the development of subsequent skin cancer in Taiwanese subjects, and the risk wanes 5 years later. Implications for Practice In this Taiwan nationwide cohort study, there was a 2.45‐fold increased risk of developing new‐onset skin cancers for patients with incident human papillomavirus (HPV) infection, compared with the matched controls. Furthermore, the risk was noticeably significant among patients aged >40 years. A prominent risk of skin cancers was found in the group diagnosed with HPV within the first 5 years after the index date in this study. The results of this analysis may raise consensus on the effect of HPV infection on the risk of skin cancers. Clinicians are encouraged to implement prudently on the differential diagnosis of skin cancers and HPV prevention and treatment, especially in older patients.

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“…Acral melanomas, also known as acral lentiginous melanomas, develop on non-hair-bearing skin, including the palms of the hands, the soles of the feet, or under the nails (34). The clinicopathological characteristics of acral melanomas differ significantly from those of cutaneous melanomas, with acral melanomas being more aggressive than cutaneous melanomas, regardless of the ancestry of patients (35). Importantly, patients with acral melanoma tend to be older and have fewer atypical nevi and a lower incidence of sunburn than patients with cutaneous melanoma (26).…”

Section: Acral Melanoma Clinicopathological Characteristicsmentioning

confidence: 99%

“…Importantly, melanoma thickness (Breslow depth) and ulceration are among the most significant factors associated with poor survival outcomes (37,38). However, the higher tumor thickness and ulceration rates in Asian patients with melanoma compared with their Caucasian counterparts may reflect differences in the clinicopathological characteristics of acral and cutaneous melanomas, such as the higher aggressiveness of acral melanomas (35). In a recent study of 1157 Chinese patients with acral melanoma, Wei et al (39) showed that patient prognosis varied depending on the anatomical location of the primary tumor.…”

Section: Acral Melanoma Clinicopathological Characteristicsmentioning

confidence: 99%

Immunotherapy in Acral and Mucosal Melanoma: Current Status and Future Directions

Mao

Zhang

et al. 2021

Front. Immunol.

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Acral and mucosal melanomas are extremely rare in Caucasians; however, they are the predominant melanoma subtypes in Asians and other non-Caucasian populations. Acral and mucosal melanomas share many clinicopathological features, including aggressive phenotypes, similar genetic landscapes, and grim prognoses. In spite of advances in melanoma management, patients with acral and mucosal melanomas show limited benefit from current therapies. The rarity of these subtypes of melanoma is a significant factor contributing to the poor understanding of these pathological subtypes and the lack of effective interventions. Furthermore, the mechanisms contributing to disparities between different types of melanoma remain largely unclear. Herein, we comprehensively review current knowledge on the clinicopathological characteristics and mutational landscapes of acral and mucosal melanomas, as well as providing an overview of current therapies for patients with these aggressive melanoma subtypes, focusing on available immunotherapeutic interventions. We also discuss pathological differences between different melanoma subtypes and summarize current knowledge on melanoma disparities between Asians and Caucasians. Finally, we discuss emerging immunotherapeutic strategies for the treatment of acral and mucosal melanomas, focusing on combination therapies with immune checkpoint inhibitors. Unraveling the unique features of acral and mucosal melanomas is key for their early diagnosis and for the development of effective therapies.

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Acral lentiginous melanoma: Basic facts, biological characteristics and research perspectives of an understudied disease

Cited by 84 publications

References 104 publications

The Molecular Landscape of Primary Acral Melanoma: A Multicenter Study of the Italian Melanoma Intergroup (IMI)

The Molecular Landscape of Primary Acral Melanoma: A Multicenter Study of the Italian Melanoma Intergroup (IMI)

The Impact of Human Papillomavirus Infection on Skin Cancer: A Population-Based Cohort Study

Immunotherapy in Acral and Mucosal Melanoma: Current Status and Future Directions

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