Practice Essentials
Malignant melanoma is a neoplasm of melanocytes or a
neoplasm of the cells that develop from melanocytes. Although it was once
considered uncommon, the annual incidence has increased dramatically over the
past few decades. Surgery is the definitive treatment for early-stage melanoma,
with medical management generally reserved for adjuvant treatment of advanced
melanoma.
Essential update: FDA approves trametinib/dabrafenib combo
for treating advanced melanoma in patients with BRAF mutations
The FDA has approved a combination of trametinib (Mekinist),
a MEK inhibitor, and dabrafenib (Tafinlar), a BRAF inhibitor, for the treatment
of patients with unresectable or metastatic melanoma and BRAF V600E or V600K
mutations. Accelerated approval was granted based on response rate and duration
in a randomized, phase 2, open-label study, in which patients who received
combination treatment had an overall response rate of 76%, compared with 54%
for those who received only dabrafenib. Median duration of response was longer with
combination treatment (10.5 vs 5.6 months). These results, reported by the
investigators, were superior to those reported by a blinded independent
radiologic review committee.[3, 4]
Signs and symptoms
The history should address the following:
Family history of melanoma or skin cancer
Family history of irregular, prominent moles
Family history of pancreatic cancer or astrocytoma
Previous melanoma (sometimes multiple; patients have
reported as many as 8 or more primary melanomas)
Previous sun exposure
Changes noted in moles (eg, size, color, symmetry, bleeding,
or ulceration)
History or family history of multiple nevus syndrome
Physical examination includes the following:
Total-body skin examination, to be performed on initial
evaluation and during all subsequent visits
Serial photography, epiluminescence microscopy, and
computerized image analysis, to be considered as adjuncts
Skin examination involves assessing the number of nevi
present and distinguishing between typical and atypical lesions. (The images
below depict examples of melanomas.) Early melanomas may be differentiated from
benign nevi by the ABCDs, as follows:
A - Asymmetry
B - Border irregularity
C - Color that tends to be very dark black or blue and
variable
D - Diameter ≥ 6 mm
If a patient is diagnosed with a melanoma, examine all lymph
node groups.
See Clinical
Presentation for more detail.
Diagnosis
The following laboratory studies are indicated:
Complete blood count
Complete chemistry panel (including alkaline phosphatase,
hepatic transaminases, total protein, and albumin)
Lactate dehydrogenase
The following imaging modalities may be considered:
Chest radiography
Magnetic resonance imaging of the brain
Ultrasonography (possibly the best imaging study for
diagnosing lymph node involvement)
Computed tomography of the chest, abdomen, or pelvis
Positron emission tomography (PET; PET-CT may be the best
imaging study for identifying other sites of metastasis)
Procedures to be considered in the workup include the
following:
Complete excisional biopsy of a suggestive lesion
Surgical excision or reexcision after biopsy
Elective lymph node dissection (ELND) for patients with
clinically enlarged nodes and no evidence of distant disease
Sentinel lymph node biopsy (SLNB; see Sentinel
Lymph Node Biopsy in Patients With Melanoma)
Characteristic histologic findings include the following:
Cytologic atypia, with enlarged cells containing large,
pleomorphic, hyperchromic nuclei with prominent nucleoli
Numerous mitotic figures
Pagetoid growth pattern with upward growth of the
melanocytes
See Workup for
more detail.
Management
Surgery (eg, wide local excision with SLNB, ELND, or both)
is the definitive treatment for early-stage melanoma. Medical management is
reserved for adjuvant therapy of patients with advanced melanoma.
Agents used in adjuvant therapy include the following:
Interferon alfa
Granulocyte-macrophage colony-stimulating factor (GM-CSF)
BRAF inhibitors (vemafurenib and dabrafenib)
Agents that may be considered for treatment of
advanced-stage (stage IV) melanoma include the following:
Dacarbazine
Temozolomide (currently used as the first-line drug for
melanoma by most oncologists)
Interleukin-2
Cisplatin, vinblastine, and dacarbazine (CVD)
Cisplatin, dacarbazine, carmustine, and tamoxifen (Dartmouth
regimen)
Imatinib mesylate[5]
Carboplatin and paclitaxel (sometimes combined with
sorafenib)
Thymosin alpha 1
Melanoma vaccines and gene therapy
Ipilimumab
Peginterferon alfa-2b[6]
The following procedures may be used to treat brain
metastases:
Stereotactic radiosurgery (for patients with a limited
number of metastases)
External-beam radiation
See Treatment and Medication for
more detail.
