Melanoma, a tumor arising from melanin-forming cells, is a primary malignancy that typically appears on the skin but can also occur in the eyes and mouth [1]. As a common form of skin cancer, melanoma impacts an estimated 97,000 individuals in the United States annually, culminating in approximately 8,000 fatalities each year [2]. The disease’s etiology is multifaceted, with critical contributing factors comprising race, regional sun exposure, and age. Remarkably, white individuals exhibit a risk of developing melanoma that is 20 times greater than that of other racial groups. Furthermore, men over the age of 65 are twice as likely as women to receive a melanoma diagnosis. Additionally, regions with elevated levels of sun exposure, such as Australia, have been found to have the highest incidence cases of melanoma globally [1]).
The first known description of melanoma can be traced back to the ancient writings of Hippocrates, indicating the disease’s long-standing presence throughout human history [3]. In modern society, its prevalence is especially prominent among young adults, particularly women, making it the most common form of cancer in this demographic [5]. The societal and economic implications of this widespread disease are profound: Each year in the United States, an estimated 5 million people receive treatment for melanoma, translating to a staggering annual cost of $8.1 billion [4]. These figures underline the imperative need for ongoing research into prevention, early detection, and efficient treatment strategies to mitigate the burden of this prevalent and life-threatening condition.
Melanoma is frequently identified through the observation of progressively pigmented, anomalous cutaneous lesions. To effectively discern malignant melanocytic lesions from benign dermatological conditions, healthcare practitioners often employ the “ABCDE” mnemonic: asymmetry, border irregularity, color variation, diameter enlargement, and evolution over time [5].
Understanding the characteristics of suspicious lesions is merely the first step in a multifaceted diagnostic and treatment process. Transitioning from lesion identification, the next critical component in managing melanoma involves staging the disease. With each stage bearing significant implications for patient prognosis and treatment strategy, melanoma’s progression can be delineated into four stages that denote the extent and severity of the disease. Stage 0 melanoma, commonly referred to as melanoma in situ, is marked by neoplastic growth confined exclusively to the epidermis, the skin’s outermost layer. In this initial stage, the abnormal cells have not yet penetrated deeper layers, such as the dermis or subcutaneous tissue, indicating that the disease has not spread beyond its point of origin. In Stage 1, the malignant melanocytes have penetrated beyond the skin’s outermost layer into the underlying dermis. This stage is characterized by increased tumor thickness compared to Stage 0, attributable to the vertical growth phase behavior of the neoplastic cells.
Though Stage 2 is also identified by continued confinement of the malignancy to the dermis, the defining features of this stage include the increased tumor thickness and the presence of ulceration (an erosive process that disrupts the epidermis), creating an open wound on the skin surface. Given the melanoma’s deeper infiltration in this stage, the probability of metastasis, i.e., the dissemination of cancerous cells to disparate regions of the body, is significantly increased [6]. In Stage 3, the malignancy extends to the regional lymph nodes, requiring a more aggressive disease course and mandating immediate therapeutic interventions. By Stage 4 melanoma, the metastatic dissemination extends beyond its initial site to distant organs. As depicted in the lower-right corner of Figure 1, this may encompass crucial organs such as the brain, liver, and lungs, marking a pivotal milestone in the progression of the disease [6]. Typically linked with an unfavorable prognosis, this stage demands a comprehensive, multifaceted, and systemic therapeutic strategy.
The management strategies of melanoma vary in severity, comprising a wide spectrum of treatment from local surgical interventions to more advanced, systemic modalities. At the initial stages (0-2), surgical excision is primarily employed; this involves the resection of the neoplastic growth and an appropriate margin of the surrounding healthy dermis [7]. Upon progression to stages 2-3, when the malignancy becomes more aggressive, immunotherapy is considered. This methodology hinges on the principle of augmenting innate immunological mechanisms to effectively counter neoplastic cells. Therapeutic agents are typically administered intravenously, specifically engineered to target proteins expressed on the neoplastic cells. There are several subdivisions of immunotherapy including, but not limited to, immune checkpoint inhibitors, interleukin-based therapies, and oncolytic virotherapy [7].
Immune checkpoint inhibitors augment the cytotoxic potential of white blood cells by targeting and neutralizing inhibitory proteins that would otherwise impede these immune cells from effectively eradicating the malignant entities [8]. On the other hand, interleukin immunotherapy involves the administration of interleukins, essential modulators of white blood cell activity, thereby attenuating the growth and proliferation of melanoma tumors. Oncolytic virotherapy utilizes genetically modified viruses, selectively designed to target and eliminate neoplastic cells. These immunotherapeutic interventions are not solely restricted to active stages of the malignancy but are also instrumental in maintaining immunological durability during the convalescent phase post-melanoma treatment [7]. Targeted molecular therapy is also a formidable contender as a management method for melanoma. This strategy involves the inhibition of the mutated BRAF gene, a frequent genetic aberration in melanoma that precipitates anomalous and unregulated cellular proliferation. Lastly, radiotherapy remains an indispensable tool in managing melanoma. This modality operates by delivering high-energy radiation, specifically directed towards the loco-regional tumors, thus effectively compromising the DNA integrity within the malignant cells and precluding further propagation of the disease [6].
Therapeutic approaches toward melanoma remain an enigmatic challenge. Current cancer treatments suffer from significant drawbacks.. These can range from gastrointestinal disturbances such as nausea to hematological complications, compromised immunity, and an increased predilection for other illnesses [9]. Even in the aftermath of successful treatment, the shadow of re-emergence looms, with melanoma documented to re-emerge anywhere between 5 and 25 years post-treatment [1]. Furthermore, there is another formidable, socioeconomic barrier: the costs of melanoma treatments, which vary greatly depending on the stage of the disease, can be prohibitive. Treatment expenses can range from $400 for early-stage melanoma to an astronomical $50,000 for advanced stages [10]. This significant financial burden furthersthe issue, making access to potentially life-saving treatments challenging for many individuals.
Sources
[1]https://www.mayoclinic.org/diseases-conditions/melanoma/symptoms-causes/syc-20374884#:~:text=Melanomas%20can%20develop%20anywhere%20on,your%20hands%20and%20fingernail%20beds.
[2] https://www.cancer.org/cancer/types/melanoma-skin-cancer/about/key-statistics.html
[3] https://www.ncbi.nlm.nih.gov/books/NBK13962/
[4]https://www.skincancer.org/skin-cancer-information/skin-cancer-facts/#:~:text=The%20annual%20cost%20of%20treating,and%20%243.3%20billion%20for%20melanoma.
[5]https://www.cdc.gov/cancer/skin/basic_info/symptoms.htm#:~:text=Border%3A%20Is%20the%20border%20irregular,past%20few%20weeks%20or%20months%3F
[6] https://www.aimatmelanoma.org/stages-of-melanoma/
[7] https://www.pennmedicine.org/cancer/types-of-cancer/melanoma
[8] https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors
[9] https://www.mskcc.org/cancer-care/types/melanoma/treatment/radiation-therapy-melanoma
[10] https://healthmatch.io/skin-cancer/cost-of-skin-cancer-treatment