Melanoma, the most lethal form of skin cancer, involves the melanocytes in the basal layer of the epidermis. There is an abnormal growth of melanocytes which are unable to respond appropriately to regulatory cues from the keratinocytes as a result of a mutation in the genes that regulate cell growth. The lesion may originate as a nevus or mole which is formed when there is an overlap in growth involving both the epidermis and dermis[i] or it may originate from transformed stem cells, in which case the melanoma may be resistant to treatment.[ii] A melanoma can also occur as a new, abnormally appearing mole or freckles. When two or more moles are adjoining, they may appear similar to a melanoma and are termed “collision nevi.”
Melanoma occurs most frequently in anatomical areas that are exposed to ultraviolet rays from the sun or from tanning beds, but can also occur in the eyes, nails, genitals, and non-sun exposed areas. They present in the following descriptive types:
- Superficial spreading malignant melanoma
- Nodular melanoma
- Acral lentiginous melanoma (occurs on the palms, soles, under the nails, or in the oral mucosa, most commonly in people with darker skin)
- Minimal deviation melanoma (uncommon nevomelanocytic tumors that appear as pigmented or nonpigmented skin nodules; clinically diagnosed as Spitz nevi, hemangiomas, or malignant melanomas)[iii]
- Desmoplastic melanoma (usually occurs on the head and neck of individuals with sun-damaged skin)
- Amelanotic melanoma (lacks typical pigmentation of most melanomas, and can mimic SCC, BCC, or other nodular red cancers)
The clinical appearance of melanoma is best described by the ABCDE presentation:
- Asymmetry of the discolored area
- Borders that are uneven and distinct
- Color that is dark brown or black (Amelanotic melanomas can defy this characteristic)
- Diameter more than 1 cm
- Evolution to a larger, darker lesion
Melanomas are classified by depth according to the Breslow and Clark Depth Scales:
- Stage I - ≤0.75mm; confined to the epidermis (in situ)
- Stage II – 0.75mm-1.5mm; invasion into papillary dermis
- Stage III – 1.51mm-2.25mm; fills papillary dermis and compresses the reticular dermis
- Stage IV – 2.05mm-3.0mm; invasion of reticular dermis (lacoalized)
- Stage V - >3.0mm; invasion of subcutaneous tissue (regionalized by direct extension)[iv]
Any lesion suspicious of being a melanoma is first confirmed or negated by a surgical or shave biopsy to at least determine the dermal layer, with care for the biopsy to obtain the entire area of concern because partial biopsies may yield false negative results. A Pigmented Lesion Assay (PLA) is a non-invasive diagnostic method that uses an adhesive patch to obtain mRNA from the surface of a suspected melanoma, and may be used in lieu of a biopsy.[v] myPath Melanoma is a diagnostic test that measures the expression of 23 genes in a suspicious lesion in order to distinguish a malignant melanoma from a benign nevus. DecisionDx-Melanoma test is a gene profile test to help determine recurrence or metastasis of melanoma. Because of the validity and specificity of these tests, genetic testing is advised for patients who have a strong familial history of melanoma.[vi]
Once a positive diagnosis is confirmed, treatment involves wide local excision, followed by sentinel node biopsy, chemotherapy, and radiation if needed. The results of the sentinel node biopsy and the Breslow thickness are strongly predictive of prognosis/survival for patients with a melanoma.[vii] Mohs surgery with immunohistochemistry or slow Mohs may be used for melanoma in situ, thin melanomas, or lentigo maligna.
No wound management is indicated unless the excision results in a non-healing wound, in which case standard moist wound therapy is advised. Use of any biophysical agents (electrical stimulation, ultrasound) would be contraindicated.
In summary, any patient with an abnormal skin appearance that is suspicious of being a melanoma based on the ABCDE characteristics should be referred emergently to a qualified dermatologist or plastic surgeon for immediate diagnosis and treatment.
[i] Mabeta P. Paradigms of vascularization in melanoma: Clinical significance and potential for therapeutic targeting. Biomedicine & Pharmacology. 2020;127. Available at https://doi.org/10.1016/j.biopha.2020.110135.
[ii] Wickremesekera HD, Brasch VM, Lee PF, Davis K, Woon K, Johnson R, et al. Expression of cancer stem cell markers in metastatic melanoma to the brain. J Clin Neurosci. 2019;60:112-116.
[iii] Muhlbauer JE, Margolis RJ, Mihm MC, Reed RJ. Minimal deviation melanoma: A histologic variant of cutaneous malignant melanoma in its vertical growth phase. J Invest Dermatol. 1983;80 Suppl:63s-65s.
[iv] Breslow thickness. Available at https://www.rcpa.edu.au/Library/Practising-Pathology/ICCR/docs/ICCR_Melanoma_Breslow. Accessed June 15, 2020.
[v] Ferris LK, Rigel DS, Siegal DM, Skelsey MK, Peck GL, Hren C, et al. Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month follow-up of negative test results and utility data from a large US registry study. Dermatol Online J. 2019;25:5. Pii:13030/qt61w6h7mn. Accessed April 29, 2020.
[vi] Fried BS, Tan A, Bajaj S, Liebman TN, Polsky D, Stein JA. Technological advances for the detection of melanoma: Part II. Advances in molecular techniques. J Am Acad Dermtol. 2020. Available at https://doi.org/10.1016/j.jaad.2020.03.122. Accessed April 29, 2020.
[vii] Thomson DR, Rughani MG, Kuo R, Cassell OCS. Sentinel node biopsy is strongly predictive of survival in cutaneous melanoma: Extended follow-up of Oxford patients from 1998-2014. J Plastic, Reconstructive, Aesthetic Surg. 2017;70(10):1397-1403.