Melanoma in Adult
See also in: Anogenital,Hair and Scalp,Oral Mucosal LesionAlerts and Notices
Synopsis

Melanoma is an aggressive malignancy of pigment-producing cells known as melanocytes. Melanoma may arise at sites of melanocytes including on the skin, on mucous membranes, around the nail apparatus (see nail melanoma), and in the eye. There are 4 main subtypes of melanoma: superficial spreading melanoma (the most common type), nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma (the least common type).
The etiology of melanoma is incompletely understood, although ultraviolet radiation is believed to play a role in some melanomas and knowledge of the melanoma genome continues to advance. Melanoma susceptibility genes have been associated with melanoma tumor syndromes and some other familial tumor syndromes; these include mutations in CDKN2A/CDK4 (familial atypical multiple mole melanoma syndrome [FAMMM syndrome]), BAP1 (BAP1 cancer syndrome), MITF (MITF tumor syndrome), TERT/Shelterin complex, and PTEN). Melanoma has been shown to have one of the highest mutation rates of any cancer type, reflective of its clinical and pathologic diversity and resistance to treatment in advanced stages.
Risk factors for melanoma include a family history or prior personal history of melanoma, a history of severe or blistering sunburns, a changing mole, a giant congenital nevus (greater than 20 cm), older age, lighter skin phototype, and multiple atypical nevi. In a case control study of over 1000 patients, 3 or more iris pigmented lesions conferred an increased risk for cutaneous melanoma. Men are more prone to developing melanoma on the head, neck, and trunk, whereas women tend to develop melanoma on the arms and legs. Parkinson disease is associated with an increased risk of melanoma. The median age at diagnosis is in the 60s. The number of new cases of melanoma in the United States has been steadily rising since 1975, with an estimated 76 380 new cases of melanoma in the United States in 2016. The lifetime risk of being diagnosed with melanoma in the United States is estimated to be 2.1%.
The primary prognostic feature of melanoma is the depth of invasion, which is measured histologically in millimeters and referred to as the Breslow thickness. Early diagnosis and treatment of thin melanomas can lead to a generally favorable prognosis (97% and 93% for 5- and 10-year survival for a T1aN0M0 melanoma; see staging below), while with advanced forms the prognostic outlook is less favorable. Mortality rates are higher among men than among women. Melanoma can metastasize to any organ of the body. The most frequent sites are skin / subcutaneous, lymph nodes, lungs, liver, and brain. Rarely, primary diffuse meningeal melanomatosis can occur.
Related topic: amelanotic melanoma
The etiology of melanoma is incompletely understood, although ultraviolet radiation is believed to play a role in some melanomas and knowledge of the melanoma genome continues to advance. Melanoma susceptibility genes have been associated with melanoma tumor syndromes and some other familial tumor syndromes; these include mutations in CDKN2A/CDK4 (familial atypical multiple mole melanoma syndrome [FAMMM syndrome]), BAP1 (BAP1 cancer syndrome), MITF (MITF tumor syndrome), TERT/Shelterin complex, and PTEN). Melanoma has been shown to have one of the highest mutation rates of any cancer type, reflective of its clinical and pathologic diversity and resistance to treatment in advanced stages.
Risk factors for melanoma include a family history or prior personal history of melanoma, a history of severe or blistering sunburns, a changing mole, a giant congenital nevus (greater than 20 cm), older age, lighter skin phototype, and multiple atypical nevi. In a case control study of over 1000 patients, 3 or more iris pigmented lesions conferred an increased risk for cutaneous melanoma. Men are more prone to developing melanoma on the head, neck, and trunk, whereas women tend to develop melanoma on the arms and legs. Parkinson disease is associated with an increased risk of melanoma. The median age at diagnosis is in the 60s. The number of new cases of melanoma in the United States has been steadily rising since 1975, with an estimated 76 380 new cases of melanoma in the United States in 2016. The lifetime risk of being diagnosed with melanoma in the United States is estimated to be 2.1%.
The primary prognostic feature of melanoma is the depth of invasion, which is measured histologically in millimeters and referred to as the Breslow thickness. Early diagnosis and treatment of thin melanomas can lead to a generally favorable prognosis (97% and 93% for 5- and 10-year survival for a T1aN0M0 melanoma; see staging below), while with advanced forms the prognostic outlook is less favorable. Mortality rates are higher among men than among women. Melanoma can metastasize to any organ of the body. The most frequent sites are skin / subcutaneous, lymph nodes, lungs, liver, and brain. Rarely, primary diffuse meningeal melanomatosis can occur.
Related topic: amelanotic melanoma
Codes
ICD10CM:
C43.9 – Malignant melanoma of skin, unspecified
SNOMEDCT:
372244006 – Malignant melanoma
C43.9 – Malignant melanoma of skin, unspecified
SNOMEDCT:
372244006 – Malignant melanoma
Look For
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Diagnostic Pearls
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Differential Diagnosis & Pitfalls
- Atypical nevus
- Seborrheic keratosis – presence of pseudo-horn cysts is typical
- Pigmented basal cell carcinoma – pearly quality
- Squamous cell carcinoma in situ (Bowen disease, pagetoid or pigmented)
- Spitz nevus
- Compound nevus
- Congenital nevus
- Blue nevus
- Lentigo simplex
- Solar lentigo
- Lobular capillary hemangioma (pyogenic granuloma) – friable, glistening surface
- Angiokeratoma
- Hemangioma – cherry, thrombosed
- Dermatofibroma – firm, tan or brown papule with positive dimple sign
- Halo nevus – tan or brown papule with surrounding depigmented patch
- Metastatic carcinoma
- Paget disease
- Tinea nigra
- Subungual hematoma
- Pigmented actinic keratosis
- Talon noir (black heel)
- Longitudinal melanonychia (a pigmented line along the length of a nail plate) may be a benign finding or a sign of a nail matrix melanoma. Hutchinson's sign – the presence of pigment in the proximal nail fold in a patient with longitudinal melanonychia – should prompt consideration of a nail matrix melanoma.
- Recurrent melanocytic nevus – History of the initial biopsy is often critical for the dermatologist and/or pathologist. Recurrent nevi characteristically occur on the trunk within 6 months of the original biopsy in women aged 20-30 years. While many different clinical morphologies may be seen, it often manifests as a scar with variegated hyper- or hypopigmentation, linear streaking, and halo, stippled, and/or diffuse pigmentation patterns. While most cases do not pose a diagnostic challenge on histopathology, some specimens, especially partial biopsies, may look indistinguishable from melanoma on histopathologic grounds alone.
Best Tests
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Management Pearls
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Therapy
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Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.
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References
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Last Reviewed:06/13/2022
Last Updated:05/31/2023
Last Updated:05/31/2023

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Melanoma in Adult
See also in: Anogenital,Hair and Scalp,Oral Mucosal Lesion