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Additional risk assessment may be beneficial for patients with acral lentiginous melanoma


Multivariable regression determined acral lentiginous melanoma (ALM) comprised 1.6% of all CM and had the highest risk for a positive SLN (rate of positivity: Stage 1B, 18.39%, 95%CI 13.82-24.03%; Stage II 39.53%, 95%CI 34.98-44.26%).

Clinical Pearls

  • This retrospective cohort study assessed American Joint Commission on Cancer 8th Edition (AJCC8) stage I and II cutaneous melanomas (CM) from the National Cancer Database (NCDB) between 2012-2015 to determine factors that were associated with positive sentinel lymph node biopsy (SLNBx).

  • Of the 60,148 patients with malignant melanoma identified, multivariable regression determined non-superficial spreading subtypes were nearly twice as likely to have a positive SLNBx (Odds Ratio 1.91, 95% confidence interval 1.59-2.28). Acral lentiginous melanoma (ALM) comprised 1.6% of all CM and had the highest risk for a positive SLN (rate of positivity: Stage IB, 18.39%, 95%CI 13.82-24.03%; Stage II 39.53%, 95%CI 34.98-44.26%).

  • ALM may display aggressive malignant behavior not captured by current clinicohistopathological factors.


Discussion:

7650 Americans are expected to die from cutaneous melanoma (CM) in 2022 alone while 1 in 44 Americans will be diagnosed with CM at some point in their lifetime. Given CM is one of, if not the most, lethal forms of skin cancer early intervention is the cornerstone of care. However, despite improvements in detection and public awareness, CM may be mis- or underdiagnosed, notably rarer subtypes such as acral lentiginous melanoma (ALM), especially among persons with darker skin phototypes and lower socioeconomic status. This delay in diagnosis may have severe consequences for patients’ morbidity and mortality.


In this retrospective cohort study, cases of American Joint Committee on Cancer 8th edition (AJCC8) clinical stage I-II CM (i.e., excluded if: in-situ, had known distant metastases, missing Breslow depth, lacked mitotic rate, lacked ulceration information, lacked decision making regarding or information from a performed sentinel lymph node biopsy (SLNBx)) diagnosed between 2012-2015 from the National Cancer Database (NCDB) were identified and stratified by subtype into superficial spreading (SSM), lentigo maligna melanoma (LMM), nodular (NM), acral lentiginous (ALM) or not otherwise specified (NOS).


In total 60,148 patients were included in the multivariable regression analysis, of which 37.4% did not have a SLNBx performed. Notably, patients with ALM were older (median age 79 v. 65, p<.001), had fewer comorbidities and were more likely to be treated at a non-academic center (p=.003). When controlling for age, sex, histologic subtype, Breslow depth, ulceration, and mitotic activity, only ALM had an increased risk for SLNBx-positivity (OR: Stage IB 2.01, 95%CI 1.41-2.87; Stage II 1.59, 95%CI 1.28-1.97) while LMM stage IB (OR 0.56, 95%CI 0.39-0.81) and stage II (0.67, 95%CI 0.49-0.91) and NM stage II (0.83, 95%CI 0.75-0.92) had a decreased risk.


ALM patients with a negative SLNBx had the best prognosis with 1-year survival of ~98.5% and 3-year survival of 82.2% (stage II) to 88.5% (stage IB) while those with a positive SLNBx had worse prognoses for stage IB and stage II disease at 1 year (96.4% and 94.7% respectively) and 3 years (76.2% and 65.4% respectively)(p<.01). Interestingly, while patients who did not have a SLNBx performed had intermediate survivals overall (1-year 94.8%; 3-year 72.8%), they had worse 3-year survival independently for stage IB (66.9%) and II (60.9%) disease and worse 1-year survival (89.9%) for stage II ALM than patients who underwent SLNBx(p<.01).


The authors conclude that ALM may have underlying biological characteristics that predispose to more aggressive characteristics are not typically captured by traditional clinicohistological factors, especially given their decrease propensity for BRAF mutations and increased incidence of KIT and CDK mutations relative to others CM subtypes. Given these findings, additional clinical scrutiny and testing may be warranted for patients with ALM, especially for patients who are not candidates for, or do not wish to undergo, SLNBx.

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