Underreporting of acral lentiginous melanoma in studies informing American Joint Committee on Cancer Staging System Guidelines: a review of 150 cited studies

Acral lentiginous melanoma (ALM) has the highest mortality rate compared with other cutaneous melanoma subtypes, with a 5-year melanoma-specific survival rate of 80.6%, compared with 93.0% for cutaneous melanomas, as reported in a Surveillance, Epidemiology, and End Results (SEER) Program study 2006–2015 (P < 0.001). The SEER study also showed that ALM disproportionately impacts patients of color, representing 34% of all cutaneous melanomas in non-Hispanic blacks, 23% in Asians, 9% in Hispanic whites and 1% in non-Hispanic whites [1]. Despite ALM exhibiting distinct clinical and genetic features from other melanoma subtypes, most melanoma research has focused on superficial spreading melanoma (SSM) and nodular melanoma [2]. Consequently, it has been proposed that distinct guidelines are needed for ALM staging and management that differ from the melanoma guidelines established by the American Joint Committee on Cancer (AJCC) [3]. In this study, we sought to quantify histological subtype reporting and ALM representation in studies used to inform AJCC staging system guidelines. We reviewed the 150 cited studies in the AJCC eighth edition staging manual on cutaneous melanoma. Randomized controlled trials (RCT) and retrospective and prospective studies were included. We extracted the study type, year of study, country of study participants, number of patients and histological subtype. A total of 121 (80.1%) studies met the inclusion criteria. Nineteen (15.7%) of these studies were RCTs, and 103 (84.3%) were retrospective or prospective. Thirty-four (28.1%) studies reported the histological subtypes of participants’ melanomas. Twenty-seven (22.31%) reported SSM, 24 (19.8%) reported nodular melanoma, 21 (17.4%) reported lentigo maligna melanoma and 15 (12.4%) reported ALM. Among the studies that reported histological subtypes, 24 221 (61.9%) of patients had SSM, followed by 3018 (7.7%) with nodular melanoma, 2696 (6.9%) with lentigo maligna melanoma, 597 (1.5%) with ALM and 8622 (22.0%) were categorized as ‘unknown’ or ‘missing’. Some studies categorized melanomas as polyploid (N = 83), occult (N = 35) or dysplastic (N = 20). The majority of the studies (97.5%, N = 118) included participants from predominantly White countries (USA, Canada, Australia or European countries). One study included patients from South America (Brazil), and two randomized clinical trials included centers in Mexico, South Africa and Africa. No study included Asian or Middle Eastern countries. We found that the vast majority (87/121, 71.9%) of melanoma studies failed to report the histological subtype and that ALM was reported in only 15/121 (12.4%) of studies. The lack of histological reporting impedes the ability to differentiate the biological, clinical and molecular characteristics of melanoma subtypes. Additionally, it makes it difficult to determine the generalizability of the AJCC guidelines for all melanoma subtypes. Among the studies that reported histological subtypes, ALM represented about 1.5% of all melanomas. This proportion is comparable to the incidence of ALM in the USA, which was reported as 1.9% of cutaneous melanomas in the SEER registry data, 2006–2015 [1]. However, ALM prevalence varies across racial and ethnic groups. Specifically, ALM represents about 3% of melanomas in populations of European descent, whereas it represents about 40% and 20% in Asians and Latin Americans, respectively [4]. The low rate of ALM participants in these studies is likely a reflection of the inclusion of studies from countries with predominantly White populations. In a 2023 commentary, Sharma et al. [5] describe barriers faced by researchers in low-income countries, including a high editorial bar for international research, and suggest solutions applicable in melanoma research, including editorial support for non-native language authors and fostering international collaborations and mentorship. The WHO predicts a 49.0% increase in melanoma cases in the USA between 2020 and 2040, and as the USA becomes more racially and ethnically diverse, ALM will likely constitute a larger proportion of these cases [4]. In a SEER analysis from 1975 to 2016, non-Hispanic whites experienced the most significant improvements in melanoma survival compared with minority groups. Between 2000 and 2010, the hazard ratio for melanoma-specific survival among Hispanics compared to non-Hispanic whites increased from 0.95 (95% CI, 0.86–1.06) to 1.56 (95% CI, 1.41–1.73) (P = 0.001), and in non-Hispanic blacks to non-Hispanic whites, it increased from 1.40 (95% CI, 1.20–1.64) to 1.87 (95% CI, 1.54–2.28) (P = 0.001) [6]. To address these disparities, future studies should examine histological subtypes of melanoma and include data from racially and ethnically diverse populations. This study included only RCTs and retrospective studies, which may have excluded relevant studies that did not meet these criteria. We also did not assess the quality of the studies included, which may have impacted the guidelines. In conclusion, our study underscores the need for consistent reporting of histological subtypes of melanoma and the inclusion of non-White populations in melanoma research to enhance management guidelines and therapies for melanoma in all races and ethnicities. Acknowledgements Financial disclosures: S.R.L. has served as a consultant for Hoth Therapeutics, Ortho Dermatologics, Moberg Pharmaceuticals, and Belle Torus Corporation. Conflicts of interest There are no conflicts of interest.

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