malignant melanoma

malignant melanoma
Name	Malignant Melanoma
Field	Oncology, Dermatology
Symptoms	Changing mole, new pigmented growth
Complications	Metastasis to brain, liver, lungs
Risks	Ultraviolet radiation, Dysplastic nevus syndrome, Xeroderma pigmentosum
Diagnosis	Dermatoscopy, Biopsy
Treatment	Wide local excision, Immunotherapy, Targeted therapy
Prognosis	Depends on Breslow depth, Clark level
Frequency	Increasing globally

malignant melanoma. It is a highly aggressive form of skin cancer that arises from melanocytes, the pigment-producing cells. Its incidence has been rising steadily in populations such as those in Australia, New Zealand, and North America. Early detection is critical, as advanced disease can metastasize widely and has historically been difficult to treat.

Overview

Malignant melanoma originates in the epidermis at the junction of the dermis. The classic presentation is a pigmented lesion demonstrating asymmetry, border irregularity, color variation, and diameter evolution, often summarized by the ABCDE criteria. Major histologic subtypes include superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. Research into its pathogenesis is heavily focused on mutations in genes like BRAF and NRAS, which drive uncontrolled cell proliferation.

Causes and risk factors

The primary environmental cause is exposure to ultraviolet radiation, particularly intermittent, intense exposure leading to sunburn. This risk is modulated by genetic factors; individuals with skin phototypes I or II, red hair, and numerous nevi are at higher risk. Major hereditary syndromes include familial atypical multiple mole melanoma syndrome (FAMMM), associated with mutations in CDKN2A, and xeroderma pigmentosum, involving defects in nucleotide excision repair. Other risk factors include a personal history of non-melanoma skin cancer and immunosuppression, such as in recipients of organ transplants from the National Health Service.

Diagnosis

Clinical diagnosis begins with a thorough examination, often aided by tools like dermatoscopy or confocal microscopy. The definitive diagnostic procedure is an excisional biopsy with narrow margins, performed to obtain the full Breslow depth and assess ulceration. Pathological analysis is conducted according to guidelines from the American Joint Committee on Cancer and involves evaluation of mitotic rate and tumor-infiltrating lymphocytes. For suspected advanced disease, imaging studies such as computed tomography, positron emission tomography, and magnetic resonance imaging are utilized to evaluate for metastasis.

Staging and classification

Staging follows the TNM staging system as defined by the American Joint Committee on Cancer, integrating key pathological factors. The primary tumor (T) category is determined by Breslow depth measured in millimeters and the presence of ulceration. Nodal status (N) assesses the number and characteristics of involved lymph nodes, often identified via sentinel lymph node biopsy. Distant metastasis (M) categorizes spread to organs like the lungs, liver, brain, or distant skin sites. Stages range from Stage 0 (in situ) to Stage IV (distant metastasis), with substages based on specific T, N, and M criteria.

Treatment

For localized disease, standard treatment is wide local excision with margins dictated by the Breslow depth. Management of regional lymph nodes may involve sentinel lymph node biopsy and, if positive, completion lymphadenectomy or adjuvant systemic therapy. For advanced or metastatic disease, treatment has been revolutionized by immunotherapy agents targeting CTLA-4 like ipilimumab and PD-1 inhibitors such as pembrolizumab and nivolumab, as well as targeted therapy against BRAF mutations using vemurafenib, dabrafenib, and trametinib. Research from institutions like the National Cancer Institute continues to explore combination regimens and neoadjuvant therapy.

Prognosis and epidemiology

Prognosis is most strongly predicted by the Breslow depth and ulceration status at diagnosis. Thin melanomas have an excellent prognosis, while thicker or ulcerated tumors carry a higher risk of recurrence and death. Epidemiological studies, including those by the Surveillance, Epidemiology, and End Results program, show rising incidence rates worldwide, with the highest rates observed in Australia and among populations of European descent in South Africa. Public health campaigns, such as those promoted by the American Academy of Dermatology and Cancer Research UK, emphasize sun protection and early detection to reduce mortality.

Category:Types of cancer Category:Dermatology