Given that melanoma accounts for the majority of deaths from skin cancer, this author discusses current incidence estimates, key diagnostic indicators, how to differentiate between different melanomas and essential considerations for biopsy.
An 81-year-old female presented to our clinic with left midfoot arthritis and pain. However, the physical exam also revealed longitudinal melanonychia with extension to the periungual skin as well as an irregular melanotic lesion at the tip of the left hallux. She vaguely remembered dropping something on the toe in the past but could not remember details, particularly as to how long the lesion had been there. There was no personal or family history of cancer, particularly skin cancer, and she was relatively healthy for her age, only reporting medical conditions such as arthritis, high cholesterol and hypertension.
Due to the irregular appearance of the lesion and the patient being unsure of any history of trauma, I recommended and performed a biopsy. I avulsed the nail and biopsied the melanocytic portion of the matrix via tangential shave. I also excised any extension on the periungual skin as well as the lesion at the tip of the toe.
The pathology report noted the lesions were melanoma in situ. However, due to the extensive involvement and satellite lesion, I referred the patient to oncology for a full workup. After consultation, the oncologist determined there was no need for further workup and she simply needed a degloving of the toe.
After the surgical oncologist performed the surgical degloving, the patient returned to our clinic for wound care and a possible skin graft. The patient chose to forego the skin graft and simply allow the wound to heal by secondary intention. While there was good healing via secondary intention, I noticed residual dark pigmentation periungually, which was concerning for persistent disease. After a discussion with the oncologist and pathologist on the case, who both confirmed complete excision of the melanoma, we felt this residual pigmentation was scarring from electrocautery during surgery and agreed to monitor the pigmentation over time.
Four months later, however, the lesion was still present, even after the rest of the toe healed and appeared normal. Both the patient and providers expressed concern. A follow-up biopsy revealed residual melanoma. This time, we referred the patient to the Mayo Clinic oncology department. They performed another degloving procedure and removed the residual melanoma. The patient subsequently healed with no recurrence.
A Closer Look At The Incidence, Risk Factors And Key Diagnostic Signs Of Melanoma
Melanoma is a tumor of melanocytes in the skin. While melanoma only accounts for one to five percent of all skin cancer cases worldwide, it causes the most skin cancer deaths and the incidence is increasing.1,2 More than 232,000 people are diagnosed with melanoma worldwide each year and over 65,000 will die from it.3 In 2016, the lifetime risk to develop melanoma for men was one in 33. For women, it was one in 502.4 Caucasians have a 10-fold higher risk of developing melanoma than African-Americans, Asians or Hispanics.5 The most common locations are the back in men and the arms and legs in women. It has the ability to metastasize to any organ, including the brain and heart.5
Melanoma can arise from a preexisting lesion but it can also develop de novo. To distinguish melanoma from regular nevi, remember the ABCDs of melanoma: asymmetry, border irregularity, color variation and diameter enlargement. Asymmetry and an irregular outline could mean the tumor is spreading horizontally at different rates, which differentiates it from a benign lesion, which grows symmetrically and homogenously if it grows at all.
Color variation can have quite a few meanings. Sudden darkening could mean the tumor is growing. Redness could be due to vasodilation and inflammation. A white color can represent regression or the body attacking the tumor, especially if there is a depigmented halo around it. Blue can mean the tumor is going deeper into the skin, signaling vertical growth, a sign of late disease.5
Changes in color and shape are important early signs of melanoma, and should always raise suspicion. Other changes in a pigmented lesion that suggest malignancy include scaliness, bleeding, erosion, ulceration, oozing, elevation, crusting, loss of normal skin lines, pruritis and pain/ tenderness. Ulceration and bleeding are late signs of disease, and their presence is a poor prognostic factor.5
Factors that greatly increase the risk of melanoma include a personal history of atypical moles or melanoma, a family history of melanoma, greater than 75 to 100 moles, previous non-melanoma skin cancer, giant (greater than 20 cm) congenital nevus and immunosuppression. Clinically atypical nevi, chronic tanning with UVA light, repeated blistering sunburns, freckling, fair skin, inability to tan and red or blond hair represent moderate risk factors for developing melanoma.5
A Guide To Differentiating The Types Of Melanoma
There are four main types of melanoma: superficial spreading, nodular, acral lentiginous and lentigo maligna. The first type, superficial spreading, is the most common and accounts for 70 percent of cases.5 It is most prevalent in middle-aged adults and can arise anywhere on the body, but usually occurs on the upper back of both genders and on the legs of women. Multiple colors may be present but this melanoma more frequently has a dull red color. This form of melanoma starts with a radial growth phase and transitions to vertical growth after months or years, making early diagnosis and treatment key in preventing metastasis and mortality.5
Nodular melanoma also occurs in middle-aged adults but it affects males twice as often as females.5 It occurs on any part of the body as well but it has a tendency to arise on the trunk and legs. Nodular melanoma exhibits very rapid growth, making it the most dangerous form of melanoma. Thankfully, it represents only 10 to 20 percent of melanomas.5 It is usually a dark brown/red/ black lesion that is dome-shaped, polypoid or pedunculated in appearance. Nodular melanoma also ulcerates and bleeds readily. Occasionally, nodular melanoma is amelanotic (1.8 to 8.1 percent of the time), frequently delaying diagnosis and treatment.5
Lentigo maligna, also known as “Hutchinson’s freckle,” occurs mostly on the face and neck although it can appear on the arms and legs in rare cases. Lentigo maligna starts as a large lesion but is very slow growing, taking years to grow vertically.
Other less common forms of melanoma (less than two percent) include melanoma arising from a congenital nevus, mucosal melanoma, ocular melanoma, malignant blue nevus, amelanotic melanoma and desmoplastic/neurotropic melanoma.5
Acral lentiginous melanoma should be of particular interest to podiatric physicians as it occurs mostly on the soles of the feet and terminal phalanges as well as the palms and mucous membranes. It is the most common form of melanoma in African-Americans and Hispanics, and accounts for approximately three to five percent of all cases of cutaneous melanoma.6 The sole of the foot is the most common site in non-Caucasian people. With acral lentiginous melanoma, radial growth occurs over years, making it possible to diagnose and treat the condition before it spreads and causes distal disease and death. However, misdiagnosis and delay in treatment frequently results in a poor prognosis for this type of melanoma.5,6
Acral lentiginous melanoma includes melanoma of the nail unit, which involves a pigmented band (longitudinal melanonychia) originating at the proximal nail fold. It can extend onto the periungual skin, a poor prognostic indicator, which is sometimes referred to as “Hutchinson’s sign.” In two percent of cases, acral lentiginous melanoma can present without any pigmentation at all, a form called amelanotic melanoma.6 In these cases, it will present as a rapidly growing and ulcerated red mass that may recur following nail surgery and excision. The prognosis of amelanotic melanoma is very poor.6
Melanoma of the nail unit is very rare and there is much we still do not know about it. The etiology, risks factors, epidemiology, clinical behavior, long-term outcomes and optimal treatment are not well characterized although some suggest trauma and sun exposure as likely associated risk factors.7
There are a few things we do know about nail melanoma that can aid our efforts to diagnose and treat this deadly disease. This includes the aforementioned ABCD classification scheme and its extension to ABCDEF. First, “A” stands for age. The fifth to seventh decades are the most common ages for presentation of nail melanoma. “B” stands for the brown or black discoloration, which one may see with a breadth of three mm or greater. “C” refers to a change in the nail plate or lack of change with treatment. “D” stands for “digit” with the most commonly affected digit being the hallux. “E” relates to Hutchinson’s sign or the “extension” of pigment onto the proximal nail fold or lateral nail fold. Finally, “F” stands for family or personal history of skin cancer, particularly melanoma.6
Pertinent Biopsy Considerations
Management of melanoma consists not only of proper excision but sufficient characterization of the lesion via a proper biopsy as well. After all, the results of the biopsy determine not only surgical margins but whether adjuvant therapy is necessary. Due to the fact that one lesion can exhibit areas of differing histological findings, excisional biopsy is recommended for evaluation of the entire lesion with proper characterization. The lesion excision should include one to three mm margins to facilitate the diagnosis but no more than five mm in order to ensure preservation of lymphatic drainage and enable identification of the sentinel lymph node later if necessary.1,4,5,8
Sometimes, however, excisional biopsy of the lesion is not possible or practical, and an incisional biopsy is necessary. In such cases, there is no increased risk of metastasis or decreased survival, but there is an increased risk of misdiagnosis. Accordingly, shave biopsies are not advisable as one may inadvertently transect the lesion and fail to provide the correct Breslow’s depth or Clark level, which could result in inappropriate treatment. Saucerization can achieve sufficient depth and simultaneously allow excision of the entire lesion or a significant portion. However, a punch biopsy is frequently more practical and just as effective at characterizing the lesion as long as one obtains the biopsy specimen from the thickest, darkest part of the lesion.4,5
Biopsy of the nail unit is complicated by multiple factors including: a poor interface between the papillary and reticular dermis; lack of subcutaneous fat between the nail matrix and underlying bone; the absence of a granular layer in the nail matrix; and the frequent occurrence of epidermal hyperplasia, resulting in exaggerated Breslow thickness. In fact, the mean Breslow’s depth at diagnosis is 3.1 mm with 69 percent of lesions at a Clark level IV or V.7 After all this, there is a real risk of permanent nail dystrophy after biopsy of the lesion, which may prevent some patients from even considering the biopsy.
Classically, clinicians would obtain nail unit biopsy specimens via a punch biopsy with or without nail avulsion. One would perform longitudinal excision of lateral lesions and suture any skin defect.9 More recently, the emergence of tangential shave techniques has reportedly decreased the risk of permanent nail damage. In a study by Zhou and colleagues in 2019, 75 percent of patients had a scar-free nail and complete removal of the longitudinal melanonychia with only a 13.3 percent recurrence rate.10
Once the biopsy of the lesion is complete and the Breslow’s depth/Clark level is established, the treating physician can perform therapeutic excision of the lesion along with sentinel lymph node biopsy and adjunctive therapy if necessary. The primary goal of melanoma treatment is histologically clear margins. Reconstruction is a secondary goal only after the physician has achieved complete excision of the lesion.
One determines the width and depth of excision, or surgical margins, by Breslow thickness. The general consensus is that for in situ melanoma, margins of 0.5 to one mm are sufficient with the depth of excision down to the level of the superficial subcutaneous tissue. The width and depth of excision then progress as the Breslow’s depth increases. For a Breslow’s depth of less than one mm, surgical margins should extend to one cm. For one to two mm, the margins would extend one to two cm. For greater than two mm, an excision of two cm or greater is necessary. Some suggest using wider margins, three to five cm, for a Breslow’s depth of two cm. However, studies show no significant improvement in local recurrence, recurrence-free survival or overall survival over more narrow (two cm) margins.4 Regardless, the depth of excision with more invasive melanoma should go down to deep fascia or periosteum.1 No data, however, supports further excision once one obtains clear margins.
In regard to melanoma of the nail unit, treatment classically involved amputation of the digit to obtain the necessary clear margins and the only controversy was over the level of amputation.7,11,12 Perhaps this was due to the poor prognosis of subungual melanoma with five-year survival rates ranging from 16 to 80 percent.12 New studies, however, are showing that the prognosis depends not upon the level of amputation but upon the time from initial diagnosis to surgery.11 Many studies now suggest that wide local excision with skin grafting is acceptable for in situ and minimally invasive melanoma, and possibly even safe in up to four mm thick invasive subungual melanoma.11 Once again, the goal is histologically clear margins, which one can obtain without amputation. However, after excision of the primary tumor, satellite tumors will occur around the surgical scar in up to five percent of patients.6
Although excision is the main treatment for melanoma, sentinel lymph node biopsy is sometimes necessary to determine if the patient needs adjunctive therapy. A nuclear medicine technologist performs lymphoscintigraphy by injecting radioactive technetium adjacent to the primary tumor in combination with blue dye. Perioperatively, the surgical oncologist can detect the sentinel node with a gamma probe and by identification of the blue dye in surgery.1
Sentinel lymph node biopsy is not for everyone however as it has associated complications including seroma/hematoma formation, infection, wound dehiscence, lymphocele, lymphedema and even anaphylactic reaction to the blue dye. As the risk of a positive sentinel lymph node is very low in thin melanomas, guidelines suggest that one should only obtain a biopsy when the Breslow depth is greater than one mm or when it is greater than 0.75 mm with other risk factors such as ulceration, mitoses, lymphovascular invasion, microsatellites, an absence of tumor-infiltrating lymphocytes, a Clark level IV/V, regression, or the patient’s age is less than 40 years old.2-5,13 Should the sentinel lymph node prove positive, one can then determine whether to pursue a complete lymph node dissection.
When To Consider Referral After A Melanoma Diagnosis
Melanoma is a very deadly disease so proper diagnosis and management are vital to ensure the most positive outcome for the patient. Therefore, both the biopsy and the excision should be performed by a physician who is well versed in both. Shuber and colleagues asked this question in a systematic review in 2019 and compared outcomes among general practitioners, plastic surgeons and dermatologists.8 They found that dermatologists had greater diagnostic accuracy and performed inappropriate procedures less often.
Additionally, Shuber and coworkers found that overall and disease-free survival rates were highest in lesions excised by a dermatologist.8 In fact, dermatologists completely excised lesions and had clear margins more often than general practitioners or plastic surgeons. However, plastic surgeons were more likely to excise lesions in difficult to treat areas and that may have contributed to their decreased clear margin rate. This doesn’t mean that only dermatologists should perform the procedures but it is clear the best outcomes occur when experienced physicians are involved.8
Melanoma is the most deadly form of skin cancer. Ensuring diagnosis and treatment as early as possible can help prevent metastasis and death. Performing the biopsy correctly in order to ensure proper diagnosis and extent of the disease is paramount. The main goal of treatment is complete excision of the lesion with clear margins with reconstruction being a secondary goal. If the lesion is deep, sentinel lymph node biopsy may be necessary to determine the likelihood of metastatic disease and whether adjunctive therapy is necessary. Due to the deadly nature of this disease, a physician well versed in the diagnosis and treatment of melanoma should lead the care team.
Dr. Vella completed a fellowship in podiatric dermatology and is in private practice in Gilbert and Sun City, Ariz.
1. Delgado AF, Zommorodi S, Delgado AF. Sentinel lymph node biopsy and complete lymph node dissection for melanoma. Curr Oncol Rep. 2019;21(6):54.
2. Wong SL, Faries MB, Kennedy EB, et al. Sentinel lymph node biopsy and management of regional lymph nodes in melanoma: American Society of Clinical Oncology and Society of Surgical Oncology clinical practice guideline update. J Clin Oncol. 2018;38(4):399-413.
3. Cordeiro E, Gervais M, Shah PS, Look Hong NJ, Wright FC. Sentinel lymph node biopsy in thin cutaneous melanoma: a systematic review and meta-analysis. Ann Surg Oncol. 2016;23(13):4178-4188.
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10. Zhou Y, Chen W, Liu Z, Liu J, Huang F, Wang D. Modified shave surgery combined with nail window technique for the treatment of longitudinal melanonychia: evaluation of the method on a series of 67 cases. J Amer Acad Dermatol. 2019;81(3):717-722.
11. Nakamura Y, Ohara K, Kishi A, et al. Effects of non-amputative wide local excision on the local control and prognosis of in situ and invasive subungual melanoma. J Dermatol. 2015;42(9):861-866.
12. Cochran AM, Buchanan PJ, Bueno RA, Neumeister MW. Subungual Melanoma: a review of current treatment. J Plast Reconstr Surg. 2014;134(2):259-273.
13. Gyorki DE, Barbour A, Hanikeri M, Mar V, Sandhu S, Thompson JF. When is a sentinel node biopsy indicated for patients with primary melanoma? An update of the ‘Australian guidelines for the management of cutaneous melanoma.’ Austral J Dermatol. 2017;58(4):274-277.