Melanoma (Skin Cancer): Symptoms, Diagnosis and Current Treatment Options

What is melanoma?

Melanoma develops from melanocyte cells in the skin. Besides the skin, it can also occur in the eye (uveal melanoma) and on mucosal surfaces such as the nose, mouth and anus. This article is about cutaneous melanoma, the most common form; uveal and mucosal melanoma are covered briefly below [1][6]. Non-melanoma skin cancers such as basal cell and squamous cell carcinoma follow a different course and are assessed separately [4].

What causes melanoma? Risk factors

Ultraviolet (UV) rays from the sun or from artificial sources such as tanning beds damage the DNA of cells and are one of the main causes of melanoma [2]. Many blistering sunburns, especially in childhood and adolescence, many or atypical (dysplastic) moles, fair skin, a family history of melanoma or atypical moles, a previous melanoma and a suppressed immune system increase the risk [1][2]. The risk increases with age [2][3].

How common is melanoma?

According to data from the Republic of Türkiye Ministry of Health, the incidence of melanoma in Türkiye is 1.9 per 100,000 in men and 1.2 per 100,000 in women; about 1,500 new cases are reported each year [4]. In US data the average age at diagnosis is 67; melanoma can also occur in young adults [3].

What are the symptoms of melanoma?

• A mole or spot that is new or that changes over time in size, shape or colour
• ABCDE criteria: asymmetry (the two halves do not match), irregular border, uneven colour, diameter usually larger than 6 mm (it can be smaller) and evolution (change) [5]
• A lesion that looks unlike the moles around it and stands out like an “ugly duckling” [5]
• A sore that does not heal, bleeding, crusting, itching or tenderness [5]

Melanoma can also develop in areas that do not see the sun; therefore regular checks of the whole skin, including the palms, soles, scalp and nails, are recommended [4]. When a changing or suspicious lesion is noticed, a dermatology examination should not be delayed [4][5].

How is melanoma diagnosed?

The suspicious lesion is examined with a dermatoscope. The diagnosis is made by removing the lesion completely with narrow margins (excisional biopsy) and pathological examination. Features in the pathology report such as tumour thickness (Breslow) and ulceration determine staging and the next steps [6]. When advanced disease is suspected, imaging methods such as CT, MRI or PET-CT are used [6].

Sentinel lymph node and molecular tests

In melanomas of a certain thickness and ulceration status, sentinel lymph node biopsy, which samples the first lymph node to which the tumour may spread, contributes to staging [1][6]. The MSLT-II trial showed that in patients with tumour found in the sentinel node, immediate removal of all regional lymph nodes (completion dissection) did not improve melanoma-specific survival compared with ultrasound surveillance; therefore surveillance is preferred in many patients [7]. In advanced-stage and high-risk patients, the tumour tissue is tested for a BRAF V600 mutation; other alterations such as NRAS and KIT are also assessed when needed [6].

How is melanoma treated?

The treatment plan is determined according to the stage, tumour characteristics, BRAF status and the patient’s general health. Assoc. Prof. Dr. Ali Oğul’s approach is to evaluate patient files in a multidisciplinary tumour board with specialists in dermatology, surgery, pathology, radiology and radiation oncology.

Early stage: surgery

In early-stage melanoma, the mainstay of treatment is wide excision with a safe surgical margin determined by the thickness of the tumour; sentinel lymph node biopsy is added in patients who need it [1][6].

Treatment after surgery (adjuvant)

In completely resected stage III patients, pembrolizumab [8] or nivolumab [9] can be used to reduce the risk of recurrence; in stage III patients with a BRAF V600 mutation, the combination of dabrafenib and trametinib is an option [10]. In selected stage IIB and IIC patients, pembrolizumab has been shown to reduce the risk of recurrence or death [11]. The choice is made in the tumour board together with possible side effects, accompanying diseases and the patient’s preference.

Metastatic or inoperable disease

In the first line, anti-PD-1-based immunotherapy is the mainstay: nivolumab or pembrolizumab alone; the combination of nivolumab with ipilimumab has long-term survival data, but severe side effects are more common [12]. In the combination of nivolumab with relatlimab, progression-free survival was longer than with nivolumab alone (median 10.1 versus 4.6 months) [13]. If a BRAF V600 mutation is present, BRAF and MEK inhibitor combinations such as dabrafenib with trametinib or encorafenib with binimetinib are used; the sequence of immunotherapy and targeted treatment is determined in the tumour board according to the patient [6]. In brain metastases, stereotactic radiotherapy and systemic treatment are considered together.

Progression after immunotherapy: cell therapy

In patients who progress after anti-PD-1 treatment (and a BRAF inhibitor if there is a BRAF mutation), lifileucel (TIL therapy), in which T cells obtained from the patient’s own tumour are expanded and given back, received accelerated approval from the US Food and Drug Administration (FDA) on 16 February 2024; the approval is based on an objective response rate of 31.5% in 73 patients [14]. In a randomised phase 3 trial, TIL therapy provided longer progression-free survival than ipilimumab (median 7.2 versus 3.1 months) [15]. Because this treatment requires lymphocyte-depleting chemotherapy and high-dose interleukin-2, it can be given only in centres with intensive supportive care facilities and in selected patients.

Uveal and mucosal melanoma

Uveal melanoma develops inside the eye; it is not related to UV exposure (except in the iris), differs biologically from cutaneous melanoma and is managed under a separate guideline. Metastases mostly occur in the liver; in HLA-A*02:01-positive metastatic patients, tebentafusp has a place as standard first-line treatment [16]. Mucosal melanoma is rare and can follow a different course from cutaneous melanoma [6]. These two types should be assessed in experienced centres and in a multidisciplinary way [16].

Treatment in older age

Melanoma is more common at older ages [3]. Immunotherapy and targeted treatments can also be given to older patients; the decision is made less on calendar age than on accompanying diseases, the drugs being taken, physical and cognitive function, independence in daily living and care support. When needed, a geriatric assessment is performed together with a geriatrician; immunotherapy requires special attention in those with autoimmune disease.

Access in Türkiye

The TİTCK list of licensed products dated 09.10.2026 includes products containing nivolumab, pembrolizumab, ipilimumab, dabrafenib, trametinib, encorafenib and binimetinib; products containing relatlimab and lifileucel do not appear in the list [17]. That a drug is licensed does not mean that it is reimbursed by the Social Security Institution (SGK) for every indication; coverage is verified separately from the product information and the current SGK lists.

Latest regulatory updates for this cancer type: Melanoma: Latest Developments

Side effects and follow-up during treatment

Immunotherapy can cause immune-related side effects such as diarrhoea and colitis, skin rash, thyroid and pituitary gland disorders, and inflammation of the liver or lungs; when reported early, most can be managed. With BRAF and MEK inhibitors, fever, skin and eye findings and monitoring of heart function are important. After treatment, a regular follow-up plan is arranged, including examination of the whole skin and lymph nodes and, depending on stage, imaging; because of the risk of a second melanoma, skin checks are continued for a long time [6].

Can melanoma be prevented?

Avoiding unprotected exposure during the hours when the sun is strongest (10:00–16:00), using protective clothing, a hat and sunglasses, applying a broad-spectrum, high-protection-factor sunscreen and avoiding tanning beds reduce the risk [2][4]. Although there is no clear screening guideline for early detection, a monthly skin self-examination helps changes to be noticed early [4]. Dermatology follow-up is recommended for people with many moles or a familial risk.