Melanoma overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Melanoma Microchapters
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Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Melanoma from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
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History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
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Historical Perspective

Melanoma was first described by Hippocrates in the 5th century BC. It was often described as the fatal black tumor. In 1838, the term melanoma was first proposed by Sir Robert Carswell, a British pathologist. In 1956, Henry Lancaster, an Australian mathematician, was the first to discover the association between UV radiation exposure and development of melanoma. In 2003, BRAF mutations were first identified in the pathogenesis of melanoma.

Classification

Melanoma may be classified into either cutaneous or subcutaneous melanomas. The most common 4 subtypes of cutaneous melanoma include superficial spreading melanoma, nodular melanoma, acral lentiginous melanoma, and lentigo maligna melanoma. Less common subtypes of melanoma include desmoplastic/spindle cell melanoma, nevoid melanoma, spitzoid melanocytic melanoma, angiotropic melanoma, blue nevus-like melanoma, and composite melanoma.

Pathophysiology

Development of melanoma is the result of multiple genetic mutations. The progression to melanoma usually involves the of serine-threonine kinases of the MAPK/ERK pathway (mitogen-activated protein kinase) following mutation of either the N-RAS or BRAF oncogene. On gross pathology, the majority of melanomas appear as hyperkeratotic, black-brown, asymmetric nodules with irregular borders, but the morphology of the lesion mostly depends on the subtype of melanoma. On microscopic histopathological analysis, each subtype of melanoma has unique characteristic features.

Causes

Melanoma may be caused by sporadic genetic mutations (e.g. BRAF and/or N-RAS) or may be part of familial syndromes (e.g. familial atypical multiple mole melanoma syndrome).

Differential Diagnosis

Melanoma must be differentiated from other causes of skin lesions, such as other skin cancers, premalignant skin tumors, and benign skin lesions.

Epidemiology and Demographics

The prevalence of melanoma is approximately 150-200 per 100,000 individuals. The majority of patients are diagnosed after the age of 65 years. Melanoma is more common among males and individuals of Caucasian race.

Risk Factors

The two most potent risk factors in the development of melanoma are light-colored skin and exposure to ultraviolet radiation. Other risk factors include old age, male gender, family history of melanoma, personal history of skin cancers, immunodeficiency, and certain hereditary disorders.

Screening

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for skin cancers, including melanoma.

Natural History, Complications and Prognosis

Melanoma is an aggressive tumor characterized by early metastasis. Complications of melanoma are usually related to the site of metastasis. The 5-year relative survival of patients with melanoma was 92.9%. Features associated with worse prognosis are tumor thickness (Breslow thickness), depth related to skin structures (Clark level), type of melanoma, presence of ulceration, presence of lymphatic/perineural invasion, location of lesion, presence of satellite lesions, and presence of regional or distant metastasis.

Diagnosis

History and Symptoms

Symptoms of melanoma include a rapidly growing existing nevus, non-healing skin ulcers, pruritus, or bone pain.

Physical Examination

Physical exam findings suggestive of malignant melanoma include ABCD: Asymmetry of lesion, Border irregularity, Color change, and large Diameter.

Laboratory Findings

There are no laboratory findings associated with the diagnosis of melanoma. Once melanoma is diagnosed, elevated concentration of serum lactate dehydrogenase (LDH) may be suggestive of metastasis.

Biopsy

All patients with suspected melanoma require biopsy. Findings on biopsy may distinguish the subtype and the stage of melanoma.

Staging

Staging of melanoma is essential to determine the prognosis. Staging is based on the 2010 AJCC TNM Classification and is divided into stage 0 or melanoma in situ, stage 1 or invasive melanoma with good prognosis, stage 2 or high risk melanoma, stage 3 or melanoma with regional lymph node metastasis, and stage 4 or melanoma with distant metastasis.

Chest X Ray

There are no chest x-ray findings associated with melanoma.

CT

There are no CT scan findings associated with melanoma. Chest CT scan may be considered for diagnosis of metastatic lesions among patients who have been diagnosed with stage IA-IV melanoma and for secondary prevention of melanoma among patients who were previously diagnosed with Stage IIB-IV melanoma (annually for 5 years).

MRI

There are no MRI scan findings associated with melanoma. Brain MRI may be considered for diagnosis of metastatic lesions among patients who have been diagnosed with stage IA-IV melanoma and for secondary prevention of melanoma among patients who were previously diagnosed with Stage IIB-IV melanoma (annually for 5 years).

Echocardiography or Ultrasound

There are no ultrasound findings associated with melanoma.

Other Imaging Findings

There are no PET scan findings associated with melanoma. Chest PET scan may be considered for diagnosis of metastatic lesions among patients who have been diagnosed with stage IA-IV melanoma and for secondary prevention of melanoma among patients who were previously diagnosed with Stage IIB-IV melanoma (annually for 5 years).

Other Diagnostic Studies

No additional tests are recommended for the diagnosis of melanoma.

Treatment

Medical Therapy

Chemotherapy is indicated for high risk melanomas (stages IIB-IV) as adjuvant therapy and for metastatic disease as first-line therapy. Several single agent and combination regimens have been studied, all with modest impact on survival. All current guidelines still recommend enrollment in clinical trials over current available regimens for patients with metastatic disease. Interferon therapy is the only regimen recommended for adjuvant therapy.

Surgery

The predominant treatment for primary melanoma is wide excision of the lesion margins. The choice of clinical margins is based on the tumor thickness. When lymph nodes are involved, complete dissection of the nodal basin is recommended.

Primary Prevention

Primary prevention of melanoma includes avoidance of sunlight and ultraviolet radiation exposure.

Secondary Prevention

The choice of work-up for secondary prevention of melanoma is based on the stage of melanoma at diagnosis. Secondary prevention includes monthly self-exams, routine dermatologic evaluations, and chest and brain imaging.