Cutaneous Melanoma Care in Low-Resource Settings: Surgical Disparities in Global Reconstructive Oncology

Abstract

Background:

Cutaneous melanoma poses a major global health challenge, with marked disparities in incidence and outcomes—especially in low- to middle-income countries (LMICs), where inadequate surveillance and systemic barriers obscure its true burden. Acral lentiginous melanoma (ALM), an aggressive and diagnostically challenging subtype, disproportionately affects darker individuals and remains understudied in low-resource settings.

Methods:

A global and regional synthesis of peer-reviewed literature, cancer registry data, and clinical outcomes was conducted, with emphasis on ALM subtype distribution, surgical access, and reconstructive capacity across diverse socioeconomic settings. South Africa’s Eastern Cape was used as a contextual case study to illustrate systemic constraints in LMICs.

Results:

Despite lower melanoma incidence in LMICs, ALM confers a disproportionate mortality burden—exacerbated by diagnostic delays and limited therapeutic options. Among Black African and Asian populations, lesions frequently affect anatomically complex sites, such as the palms and soles. In low-resource settings such as South Africa’s Eastern Cape, the absence of specialized reconstructive services amplifies surgical disparities, impeding oncological margin clearance and increasing the risk of functional loss and preventable amputation. Inadequate access to adjuvant therapies and radiotherapy infrastructure further compromises survival.

Conclusions:

The management of ALM in LMICs embodies a nexus of oncological urgency and surgical inequity. Bridging disparities demands a multifaceted approach: investment in regional cancer registries, expansion of reconstructive surgical capacity, and integration of melanoma awareness into public health frameworks. By situating ALM within broader health system deficiencies, this review advocates for equity-driven policy and infrastructure initiatives to improve global melanoma outcomes—particularly in underserved populations.

Takeaways

Question: This review addresses the disproportionate burden of acral lentiginous melanoma in low- to middle-income countries, with a focus on surgical and reconstructive inequities, particularly in African settings.

Findings: Synthesizing epidemiological data and clinical observations—especially from South Africa’s Eastern Cape—our analysis reveals advanced-stage presentation, subtype-specific disparities, and an absence of reconstructive surgical infrastructure. The synthesis underscores the urgent need for investment in oncological capacity, regional cancer registries, and strengthening of surgical systems.

Meaning: Acral lentiginous melanoma highlights the need to expand reconstructive surgical services in underserved regions, where functional restoration is essential to achieving oncological cure and improving posttreatment quality of life.

INTRODUCTION

Cutaneous melanoma (CM) represents a formidable global health challenge, with striking disparities in incidence, presentation, and outcomes that underscore urgent gaps in cancer surveillance and health system responsiveness. Despite advances in molecular diagnostics, surgical innovation, and immunotherapy, the burden of disease remains unevenly distributed, disproportionately affecting underrepresented populations in low-resource settings. The dearth of epidemiological data from these regions—exacerbated by limited cancer registries, underreporting, and infrastructural barriers—obscures the true magnitude of melanoma’s impact, impeding the development of contextually appropriate interventions.

Acral lentiginous melanoma (ALM), a biologically distinct and aggressive subtype, predominates among darker-skinned populations. Although immunogenic studies have clarified aspects of its tumor microenvironment, it remains undercharacterized in the global literature. Its late presentation and poorer prognosis demand a focused epidemiological and clinicopathological inquiry. Expanding the scope of melanoma research to encompass regional registries, such as the African Cancer Registry Network and the Latin American Cancer Registry Network (REDECAN), can better characterize geographic and ancestry-related variation otherwise masked by global averages.

The review aims to delineate the global epidemiology of CM, with particular emphasis on vulnerable populations in low- to middle-income countries (LMICs). It interrogates the intersection of ancestry, geography, and access to care, while also exploring reconstructive and surgical management challenges in low-resource environments. By contextualizing melanoma disparities within broader health system constraints, this synthesis aspires to inform equity-focused strategies that can bridge diagnostic and therapeutic gaps—ultimately advancing global melanoma outcomes through inclusive and data-driven approaches.

GLOBAL CM STATISTICS

CM is a biologically aggressive malignancy of neural crest–derived melanocytes and remains the leading cause of skin cancer mortality globally, despite comprising only 4% of all skin cancers.¹ According to the International Agency for Research on Cancer, an estimated 325,000 new cases and 57,000 deaths were recorded globally in 2020, positioning melanoma as the 23rd leading cause of cancer mortality.² Projections indicate a sustained upward trajectory with global incidence and mortality expected to reach 510,000 cases and 96,000 deaths annually by 2040 if current trends persist.³ Geographic disparities are striking: Australia and New Zealand exhibit the highest age-standardized incidence—42 and 31 per 100,000 in men and women, respectively—rendering melanoma the third most common cancer among both sexes. In 2022 alone, Australia recorded 17,756 invasive melanomas (10,374 in men and 7382 in women). Similarly, Western Europe and North America report elevated incidence, approximately 19 and 21.9 per 100,000, particularly among fair-skinned populations with substantial ultraviolet exposure² (Fig. 1).⁴

Fig. 1.

Age-standardized incidences and mortality rates of melanoma of the skin by global region in 2022. Incidence (blue) and mortality (red) rates per 100,000 population are shown. Data source: GLOBOCAN 2022 (Global Cancer Observatory).

Conversely, LMICs across sub-Saharan Africa, Latin America, and South Asia exhibit markedly lower incidence rates, typically under 1 per 100,000 population.³ Latin American countries account for a melanoma-specific incidence of less than 3 per 100,000 individuals. GLOBOCAN 2020 reported 2051 new cases of melanoma in Mexico.² However, these sparse figures are likely to reflect limited surveillance systems and a paucity of region-specific literature, rather than a genuine rarity of the disease. For instance, registries in Uganda, Zimbabwe, and Tanzania have reported measurable melanoma prevalence, although comprehensive and contemporaneous data remain limited.

Paradoxically, despite lower incidence in many LMICs, mortality rates are disproportionately elevated. In 2020, Africa accounted for approximately 2.1% of global melanoma cases but had a higher share of deaths relative to its incidence. Australia and New Zealand report an age-standardized incidence rate (ASR) of 36.5 but with a much lower mortality ASR of 3.1, corresponding to a mortality-to-incidence ratio (MIR) of just 0.085.³ Conversely, in African countries, the incidence ASR is 0.3 per 100,000, yet the corresponding mortality ASR reaches 0.2, yielding an MIR of 0.67.³ Strikingly, the MIR in Africa is nearly 8-fold higher than that observed in Australia and New Zealand, highlighting profound disparities attributed to delayed diagnosis, restricted access to specialized oncological and surgical services, and limited public and clinical awareness regarding melanoma symptoms and risk. To reiterate, in South Africa, 1777 new cases and 480 deaths were reported in 2020, resulting in an MIR of 0.27, situating the country as the 22nd highest in melanoma-specific mortality globally² (Fig. 2).⁴

Fig. 2.

ASRs of melanoma of the skin by sex and global region in 2022. Incidence rates per 100,000 population are shown separately for male (blue) and female (magenta) patients. Data source: GLOBOCAN 2022 (Global Cancer Observatory).

HISTOGENESIS AND PATHOPHYSIOLOGY OF CM

The stratum basale, the deepest layer of the epidermis, is demarcated from the dermis by the basement membrane (basal lamina). This layer houses melanocytes, the pigment-producing cells responsible for melanin synthesis and photoprotection.^5–7 CMs often begin as slow-growing lesions confined to this layer. During this radial growth phase, they are typically curable with surgical excision alone.⁸ Progression is driven by genetic alterations that disrupt regulatory control of cell proliferation, enabling transition to an expansile vertical growth phase in which the tumor breaches the basement membrane and invades the dermis.⁹ Lesions exhibiting vertical growth are associated with a markedly increased risk of metastatic dissemination.¹⁰

HISTOPATHOLOGIC SUBTYPES OF CM

CM encompasses 4 principal histopathologic subtypes: superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and ALM.⁹ Superficial spreading melanoma, constituting 75% of cases, exhibits an initial radial growth phase with lateral expansion before vertical invasion, typically manifesting as irregularly bordered pigmented macules or plaques.⁸ Nodular melanoma, representing 15%–30% of cases, lacks a discernible radial phase, demonstrating early vertical invasion and presenting as polypoid or darkly pigmented nodules.¹¹

Lentigo maligna melanoma predominates in chronically sun-exposed skin of older individuals, often evolving indolently as freckle-like macules with vertical invasion over decades.¹² ALM, although accounting for only 2%–5% of melanomas, is the predominant subtype among individuals with African or Asian ancestry, disproportionately affecting acral sites such as the palms, soles, and subungual regions. ALM also occurs in White patients with outcomes comparable to stage-matched superficial spreading melanoma, indicating that ALM is biologically distinct but not ethnicity-restricted.¹³ Notably, acral melanomas are not exclusively lentiginous: approximately 50% are lentiginous, with 35%–40% being superficial spreading and 8%–20%, nodular melanoma¹⁴ (Figs. 3, 4).¹⁵

Fig. 3.

Clinical photograph of a White patient with melanoma presenting as a pigmented cutaneous lesion. Image from the Skin Cancer Image Gallery (American Cancer Society). Used with permission from Richard P. Usatine, MD.

Fig. 4.

Clinical photograph of an African patient with acral melanoma on the plantar surface of the foot demonstrating asymmetrical pigmentation and irregular borders. Image from the Skin Cancer Image Gallery (American Cancer Society). Used with permission from Richard P. Usatine, MD.

EPIDEMIOLOGY OF ALM

ALM constitutes only 2%–3% of all melanoma cases in European and other Western populations, yet predominates among individuals of African, Hispanic/Latin American, and Asian ancestry. In several Asian countries—including China, Japan, Korea, and Taiwan—and in Latin American countries such as Mexico and Peru, ALM accounts for more than half of reported melanomas, highlighting substantial geographic and ancestral variation.¹⁶

Latin America represents a heterogenous distribution of ALM, reflective of its diverse admixture of European, Indigenous, and African genetic lineages. Precise epidemiological quantification is hindered by the limited availability of comprehensive cancer registries across the region. In nations with a predominantly European genetic background—such as Argentina—melanoma subtype patterns mirror those in Europe, with superficial spreading melanoma being most common and ALM comprising only 6% of diagnoses.¹⁷ By contrast, data from Chile revealed notable variation in anatomical presentation contingent upon healthcare access and ancestry-linked variation. Individuals of higher socioeconomic status, more frequently accessing private healthcare and possessing lower proportions of indigenous ancestry, exhibited ALM in fewer than 2% of melanoma cases, whereas lower income populations with greater indigenous ancestry and reliance on public health services demonstrate ALM rates approaching 20% of melanoma diagnoses.¹⁸ In Mexico, where European, Native American, and African ancestries are extensively admixed, ALM emerges as the predominant melanoma subtype, underscoring the interplay between ancestry and disease phenotype.¹⁹

Among Asian populations, melanoma incidence remains comparatively low; however, patients often present with more advanced disease, contributing to elevated melanoma-related mortality relative to White counterparts. ALM emerges as the predominant histological subtype in this demographic, with retrospective analyses reporting prevalence rates of 50%–61% of melanoma cases in South Korea and Singapore, respectively^20–22 (Fig. 5).¹⁵

Fig. 5.

Clinical photograph of an African patient with subungual melanoma, showing irregular brown pigmentation of the nail plate. Image from the Skin Cancer Image Gallery (American Cancer Society). Used with permission from Richard P. Usatine, MD.

IMMUNOPATHOLOGY OF ALM

The mutational architecture of ALM has become increasingly well delineated in recent years, revealing distinctive genomic alterations that differentiate this subtype from other forms of CM. Recent delineation of ALM genomics has uncovered distinctive mutations, notably within the platelet-derived growth factor pathway, where specific polymorphisms mitigate oncogenic signaling and are associated with improved survival outcomes.²³ Nevertheless, ALM demonstrates inferior responsiveness to immune checkpoint inhibitors relative to other CM subtypes, reflecting unique mechanisms of immune invasion.^24,25

Emerging evidence highlights the role of indoleamine 2,3-dioxygenase, an immunosuppressive enzyme that depletes tryptophan and accumulates kynurenine, inducing T cell dysfunction and immune tolerance. This metabolic reprogramming not only enables tumor escape but also mediates therapeutic resistance against checkpoint inhibitors, positioning indoleamine 2,3-dioxygenase as both a biomarker and a promising target for combination immunotherapy.^23–26

The immunogenetic heterogeneity of CM is underscored by variations in major histocompatibility complex (MHC) class II expression and human leukocyte antigen susceptibility alleles that shape subtype-specific immune responses.²⁷ Studies in Mexican cohorts have demonstrated an association between African ancestry and heightened immune reactivity, exemplified by increased rates of acute renal graft rejection,²⁸ suggesting parallels with the disproportionate burden of ALM in individuals of African descent. These findings implicate ancestry-linked immunogenic factors in melanoma pathogenesis and highlight the imperative for integrated genetic profiling into the development of precision immunotherapeutic strategies across diverse populations^27,28 (Fig. 6).¹⁵

Fig. 6.

Clinical photograph of an African patient with melanoma presenting as a hyperpigmented lesion on the foot. Image from the Skin Cancer Image Gallery (American Cancer Society). Used with permission from Richard P. Usatine, MD.

ALM IN SUB-SAHARAN AFRICA

Epidemiological data on ALM in Africa, though limited, consistently demonstrate a disproportionately high burden among Black African populations. In South Africa, early reports showed that the majority of melanomas in Black African patients occurred on the plantar surface, with ALM comprising 54% of these cases.²⁹ Subsequent analyses revealed that approximately 80% of melanomas in Black African patients were acral, mostly classified as ALM, with late-stage diagnosis commonly observed.³⁰ More recent registry data from the public sector reaffirm ALM as the predominant subtype in this population.^30,31 Similar trends have been reported in Togo and Tunisia, underscoring ALM’s prominence across diverse African settings.^32,33

SURGICAL AND RECONSTRUCTIVE MANAGEMENT OF CM

In low-resource settings, the management of melanoma represents a critical intersection of oncological surgery, reconstructive expertise, and health systems equity. For the surgeon, melanoma’s threat lies not only in its biological behavior but also in the technical demands of treatment. Effective oncological control requires wide local excision with histologically appropriate margins, while restoring form and function—often in weight-bearing or cosmetically sensitive areas—necessitating coordinated reconstructive expertise.³⁴

Contemporary management additionally incorporates sentinel lymph node biopsy for melanomas with a Breslow depth of more than 1 mm, with selective completion lymphadenectomy considered in cases of nodal positivity; however, the therapeutic value of completion lymphadenectomy remains debated, as evidenced by the Multicenter Selective Lymphadenectomy Trial II.³⁵ Reconstruction following excision is determined by defect size and anatomical location, ranging from primary closure and secondary intention healing to split-thickness skin grafts and local or regional flaps. Looking ahead, the goal in low-resource settings is to expand access to immunotherapy, enable margin-sparing surgical approaches in anatomically critical sites, and reduce morbidity from nodal surgery through the adoption of evidence-based, resource-appropriate care pathways.³⁵

SURGICAL AND ONCOLOGICAL SYSTEMIC INEQUITIES IN LMICS

ALM often presents at a depth and location that demands complex reconstructive solutions—such as medial plantar flaps, reverse sural flaps, composite grafts, or thumb reconstruction with toe transfer. Both the hand and foot present distinct anatomical challenges in the management of melanoma. The paucity of subcutaneous tissue in the hand places critical underlying structures near the skin surface, increasing their vulnerability to direct tumor involvement and iatrogenic injury during surgical excision.³⁶ Further complicating clinical management, achieving optimal excision margins—typically ranging from 1 to 2 cm based on tumor thickness—is often impracticable in anatomically and functionally critical regions such as the plantar surfaces and subungual areas.

These specialized services are typically concentrated in major urban centers and are often unavailable in rural or low-resource settings. As a result, the reconstructive burden highlights a critical dimension of surgical inequity, where the absence of specialized services impacts not only oncological outcomes but also postoperative function, long-term mobility, and quality of life. Inadequate access to timely, advanced reconstruction increases the risk of avoidable amputations, prolonged disability, and diminished survival—outcomes that underscore the urgent need for equitable surgical system strengthening.

South Africa, although an LMIC, presents stark internal disparities and a unique clinical landscape. Its subtropical climate and racially diverse population—from deeply melanated to fair-skinned phenotypes—produces an atypical epidemiological distribution.³⁷ More than 80% of its population identifies as Black African,³⁸ a demographic in which ALM is the most prevalent and aggressive melanoma subtype. Recent literature in South Africa demonstrates that ALM accounts for approximately 65% of melanoma cases among the Black African population, compared with 11% in the general population, highlighting a significant disparity in subtype distribution.^30,39 ALM typically presents on the soles, palms, or subungual regions—anatomical sites that hinder self-detection, delay diagnosis, complicate surgical margin clearance, and present formidable reconstructive challenges. Despite lower overall incidence of melanoma in darker skin, the disease frequently presents at more advanced stages—associated with reduced survival and more aggressive biological behavior³⁹—often ulcerated and thick at diagnosis. Management may require sentinel node biopsy; regional lymphadenectomy; or, in severe cases, limb amputation.

Significant disparities in oncological care persist, wherein, even after successful surgical intervention, access to essential adjuvant therapies—such as immunotherapy (eg, checkpoint inhibitors) or molecularly targeted agents for BRAF-mutated melanomas—remains markedly constrained by financial, infrastructural, and social barriers. Although immunotherapy represents the standard of care globally, its availability in the South African public sector is severely limited. In the absence of these efficacious modalities, clinicians frequently rely on radiotherapy and conventional chemotherapy, despite their limited effectiveness. Dacarbazine and related cytotoxic agents demonstrate only modest and transient antitumor activity, with poor objective response rates.⁴⁰ In a South African cohort, median overall survival with chemotherapy was 5 months, only marginally longer than the 2 months observed in patients receiving no systemic therapy, a difference that did not reach statistical significance (P = 0.213), highlighting the minimal therapeutic benefit.⁴⁰ Although melanoma has historically been considered relatively radioresistant, radiotherapy retains a role in improving locoregional control, particularly in patients with high-risk pathological features such as nodal metastases and in the palliative management of advanced disease. Compounding the therapeutic challenge, the scarcity of radiotherapy infrastructure—exacerbated by equipment shortages and persistent maintenance deficits—frequently results in protracted waiting periods and significant delays in the initiation of treatment.⁴⁰

These challenges are especially pronounced in South Africa’s Eastern Cape province—one of the country’s most low-resourced, predominantly rural, and underserved regions with a largely Black African population. The province’s 2 metropolitan hubs—Nelson Mandela Bay and Buffalo City—house the only multidisciplinary units capable of managing complex malignant melanoma, with Frere Hospital in Buffalo City serving as a key tertiary referral center, drawing patients from across the former Transkei and Ciskei homelands, where access to primary dermatologic and surgical services remains limited. Consequently, Frere absorbs a disproportionate burden of advanced, surgically complex melanoma, yet lacks a dedicated plastic and reconstructive surgery specialist, further straining surgical service delivery.

Despite this central role, there remains a striking paucity of published data on the demographic, ethnic, and clinicopathological profile of melanoma patients treated in this region. Research on surgical outcomes, particularly functional recovery, recurrence, disease-free survival, and overall survival, remains limited, with global evidence dominated by high-resource settings limiting applicability and contributing to persistent disparities. This illustrates the global 10/90 research gap, wherein diseases disproportionately affecting marginalized populations receive minimal investigational attention. The absence of regionally grounded data impedes surgical service planning, investments in reconstructive capacity (eg, flap surgery, lymphoscintigraphy), development of training pipelines in plastic and reconstructive surgery, and public health advocacy for earlier detection. Without these efforts, ALM will continue to reflect and reinforce entrenched oncological and structural inequities, perpetuating preventable morbidity and mortality in vulnerable populations.

THE THREE DELAYS MODEL IN MELANOMA CARE

From a global surgery perspective, the management of CM in low-resource settings is profoundly shaped by structural barriers encompassed within the Three Delays Model.⁴¹ The first delay, reflecting impediments in the decision to seek care, is driven by limited provider and public awareness, sociocultural misconceptions, and the near absence of systematic dermatologic surveillance, culminating in advanced disease at presentation. The second delay, denoting challenges in reaching care, is exacerbated by geographic remoteness, inadequate transportation infrastructure, and fractured referral networks. The third delay, representing failures within the health system to provide timely, appropriate intervention, is characterized by critical shortages in surgical and reconstructive capacity, disproportionately affecting rural and socioeconomically marginalized populations. Notably, in our setting, the absence of a dedicated plastic and reconstructive surgeon within the state hospital infrastructure has resulted in a complete lack of reconstructive surgical services, further exacerbating disparities in care delivery. Mitigating these intersecting delays is essential to improving ALM outcomes and addressing broader inequities in global melanoma care.⁴¹

CONCLUSIONS

CM remains a significant global health concern, with particularly severe consequences in LMICs. Although incidence rates are comparatively lower, mortality is disproportionately higher—largely due to delayed diagnosis, advanced disease at presentation, and limited access to both oncological and reconstructive care.

ALM, which predominates in Black African, Asian, and Latin American populations, poses distinct surgical challenges. Its predilection for high-function, anatomically intricate sites such as the palms, soles, and subungual regions complicates not only wide local excision but also subsequent reconstruction. Achieving oncological control while preserving function and minimizing morbidity demands surgical expertise, multidisciplinary coordination, and access to appropriate reconstructive options—resources that are often scarce or unavailable in low-resource settings.

The lack of adequately trained reconstructive surgeons exacerbates the problem, leading to suboptimal functional outcomes, prolonged disability, and higher mortality. Although comprehensive published data remain limited, this assertion is grounded in our clinical experience within the region, where shortages in specialized surgical capacity frequently hinder optimal oncological and reconstructive care. Expanding reconstructive surgical capacity through targeted training programs, global surgery collaborations, and investment in surgical infrastructure is critical. Simultaneously, robust cancer registries are needed to better characterize disease burden and guide resource allocation. Public health initiatives aimed at early detection and timely referral are equally essential to reduce late-stage presentations and improve overall survival. Without focused investment in surgical system strengthening, patients in low-resource settings will continue to face the dual burden of advanced disease and inadequate surgical care, limiting the potential for both cure and meaningful recovery.

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.