Overview of Acral Melanoma

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    • #13932
      Annette CyrAnnette Cyr

      We had though it important to include a special forum topic on Acral Melanoma. Although rare, comprising about 5% of all melanomas, it is important to lend a voice to this patient population and the disease. for the full article, please visit: http://www.podiatrytoday.com/acral-lentiginous-melanoma-what-sets-it-apart

      Acral Lentiginous Melanoma: What Sets It Apart? | Podiatry Today
      With diagnostic issues ranging from variations in the clinical presentation to delayed detection of lesions on the sole of the foot, acral lentiginous melanoma can be a particularly challenging
      condition, which reportedly has a staggering misdiagnosis rate between 25 to 36 percent. Accordingly, this author discusses the etiology of the condition, reviews key diagnostic clues andadvocates the benefits of dermoscopy for earlier diagnosis.

      All doctors have the challenge of detecting malignant melanoma early enough to help save lives.
      However, podiatrists frequently confront acral nevi with especially challenging appearances.
      Pigmented lesions of the sole have distinctive features that go beyond the classic A to E diagnostic criteria (asymmetry,border, color, diameter, evolving). In addition, plantar melanomas are characteristically late to get a diagnosis, have a poorer response to treatment and unfortunately, a significantly higher mortality rate in comparison to more proximal

      Although some perceive melanoma in general to be rare, the incidence of melanoma worldwide is rising dramatically and despite increased efforts at screening, mortality rates have not appreciably improved.1 In the United States, the incidence of melanoma has doubled in the last 10 years. It is currently the fifth leading cancer in men and the seventh in women. Is this an actual increase in incidence or is it due to more frequent skin biopsies? Have changes in histologic interpretation criteria led to increased diagnosis? Is the increasing incidence rate perhaps related to more intense screening? Actually, these explanations do not account for the increase in melanoma mortality rates. A study of Surveillance, Epidemiology and End Results (SEER) data from 1992 to 2004 found that the actual incidence of melanoma of all thicknesses and among all socioeconomic levels is an absolutely increasing burden from 4.7 to 7.7
      cases per 100,000 older men and from 5.5 to 13.9 cases per 100,000 females.

      Improved biopsy criteria are helping physicians make an earlier diagnosis that lessens overall mortality but this does not signify a true increased incidence of melanoma. The actual increase in melanoma incidence is most likely due to an overall increase in ultraviolet light exposure. Childhood sunburns that are intermittent and severe are strongly associated with an increased risk of melanoma while more incremental occupational exposure does not confer an increased risk. These findings support the hypothesis that melanoma risk is affected primarily by intermittent intense sun exposure, which seems to paralyze the normal immune surveillance and destruction of abnormal melanocytes. A survey of patients from an academic dermatology clinic found that exposure to indoor tanning beds was a significant risk factor for the development of melanoma and that this risk was even greater among women younger than 45 years.

      The evidence is not all bad. New immunotherapy treatment is helping to decrease disease-specific mortality rates, especially in young patients who develop melanoma. But how does melanoma develop on feet that seldom see the light of day? Sunburn in adolescence damages lifelong immune surveillance and disturbs the normal apoptosis of neoplastic cells. Genetic susceptibility helps account for melanoma in shaded areas. As many as one in 10 cases of melanoma may be linked to inherited faulty genes.People who have had one melanoma and a parent with melanoma have a 30 times higher risk than the general population of developing another melanoma.

      Differentiating Among The Types Of Melanoma In The Foot
      There are basically four types of melanomas arising in the foot: nodular, superficial spreading, subungual melanomas and the most common, acral lentiginous melanomas. Interestingly, acral lesions are not just on the foot. The acral areas include the palms, soles, volar surfaces of fingers and toes, and ungual regions. Palmoplantar skin is anatomically and histologically unique. The sole is characterized by a thick, compact cornified layer with prominent
      dermatoglyphics that consist of wide parallel ridges and narrow dermatoglyphic furrows or sulci that form loops, whorls and arches in highly individualized patterns.

      The plantar epidermal basement membrane barrier is regularly perforated by many eccrine ducts. There are about 300 plantar eccrine ostia per square inch. These passages can help melanoma penetrate deeper and subsequently facilitate metastatic spread. While we know increased overall health benefits occur with 10,000 steps per day and the average person actually walks about 5,000 steps per day, the accumulated effect of thousands of impacts of direct and shear pressures can add a significant element of risk for melanoma initiation and spread. Although 5 percent of all melanomas are located on the foot, pedal melanoma is relatively rare in Caucasians.Among
      East Asians and darkly pigmented people, acral lentiginous melanoma is the most common subtype of melanoma.

      Pedal melanoma has a poorer prognosis than melanoma in other body parts and patients are more likely to die of pedal melanoma than even proximal limb melanoma.Even though the foot receives less solar exposure, it turns out pedal melanoma is more likely to kill patients than more proximal thigh melanoma. Although the five-year survival rate for melanoma of the calf is 94 percent, the five-year survival rate for foot melanoma is only 77 percent.In addition, acral
      melanoma is associated with a significantly poorer prognosis than the other subtypes of melanomas. Researchers believe this may be due to the intrinsically aggressive behavior of pedal melanoma as well as delayed detection and diagnosis.

      Why Is Acral Melanoma More Lethal?
      Clinically, an acral lentiginous melanoma appears as a dark, brown to black, unevenly pigmented
      patch. Focal areas of tumor regression may manifest as gray-white discoloration. If a lesion
      becomes raised or becomes an ulceration, the likelihood of invasion is much higher. In addition,
      some tumors that invade along the perieccrine adventitial dermis may clinically appear flat though they have penetrated deeper to the subcutaneous adipose tissue.

      Why is acral melanoma more lethal? One reason for the prognostic difference may be the general omission of feet from general physical examinations. I remember seeing an 85-year-old gentleman with dementia who presented for foot care with a 3 cm nodular melanoma on the dorsum of his foot. He had a past medical history of a melanoma on his back and actually had an exam by his dermatologist that morning for his annual post-melanoma screening exam with his socks
      on. Older age is another risk factor. Misdiagnosed cases occur predominantly in the sixth decade, reflecting the relative frequency of underlying vascular and neurological disorders in older patients. Patients themselves are also less likely to examine all the areas of their feet as they get older. With decreased flexibility and poorer vision that may accompany aging, it is naturally more difficult to examine one’s own feet.Once the abnormality is noticeable, there is still a substantial rate of misdiagnosis. The incorrect clinical diagnosis rate of acral lentiginous melanoma is between 25 and 36 percent.

      In missed melanoma cases, original diagnoses have ranged from plantar warts to tinea nigra and talon noir.Unfortunately, we have all seen case reports of acral melanoma that masqueraded as a
      diabetic ulcer for years or a “wart” or “granuloma” that a physician removed but did not send out for definitive diagnosis.Making matters even more challenging, acral lentiginous melanomas are usually pigmented but in 2 to 8 percent of cases, they are amelanotic.This may lead to the clinical misdiagnosis of these melanomas as not only warts but traumatized calluses or even chronic paronychia. This is especially a problem with subungual amelanotic melanoma. It is interesting to note that all types of physicians have initially misdiagnosed pedal melanoma as intractable diabetic skin ulcers. These reports help explain why melanoma is a perennial topic at podiatry continuing education seminars.

      Facilitating Earlier Detection With Dermoscopy
      So what is our best defense against missed diagnosis? In addition to increasing our clinical vigilance, improving our examination skills will help detect acral lentiginous melanoma earlier. We are all well trained to practice the A through E melanoma examination checklist, which research has proven to reduce melanoma deaths. However, the A through E checklist is not sensitive enough when it comes to evaluating plantar nevi. Dermoscopy increases the sensitivity of the clinical examination by 20 percent. Madankumar and colleagues, in a recent study of acral melanocytic lesions, concluded that plantar melanocytic lesions are quite common and carry an
      increased mortality. They also noted that dermoscopy of acral lesions is an important tool for the diagnosis and management of plantar pigmented lesions. There has been a rapidly growing acceptance of dermoscopy as an examination method. Educators are currently teaching it to an increasing number of podiatrists, primary care physicians and dermatologists.

      What You Should Know About The Management Of Acral Melanoma
      Our professional charge as physicians is to be vigilant for clinically suspicious lesions and triage them to biopsy, monitoring or patient reassurance. Whether we biopsy the lesion ourselves or arrange for biopsy by others, we are at a pivotal point of care to help reduce overall mortality.

      If one chooses a total excisional biopsy, Stone and colleagues recommend a 1 to 2 mm rim of
      normal appearing skin along with a cuff of subdermal fat as the optimal technique.Once one finds
      melanoma by either the punch or total excisional technique, the authors recommend wider excision
      with surgical margins of 1 cm for tumors that are 2 mm thick or less and up to 5 cm for tumors that are over 2.1 mm in thickness. This obviously can lead to extensive tissue loss, which may require amputation.

      In general, clinicians allow plantar melanoma excision sites to granulate in as opposed to performing primary closure. Once primary healing has taken place, the use of skin grafting and flaps can help restore weightbearing function. Mohs microsurgery can minimize tissue loss but has yet to be proven effective in reducing overall patient mortality. Further patient evaluation by a melanoma specific oncology team is important to improve outcome. After a diagnosis, it is important to get a staging of the cancer so a melanoma management team can develop the most effective treatment plan.

      The Melanoma Staging Database is based on clinical experiences in over 38,900 patients with melanoma and incorporates a tumor, node, metastasis (TNM) staging system. It relies upon assessments of the primary tumor, regional lymph nodes and distant metastatic sites. The Breslow thickness primarily determines the “T” and one modifies this by the mitotic rate of the tumor. The 10-year survival rate decreases progressively from 96 percent with primary lesions < 0.5 mm thick to 54 percent with lesions 4.01 to 6 mm thick. The “N” or lymphatic node designation assesses regional lymph node spread and has a major negative impact on long-term survival. The sentinel lymph node biopsy is recommended for tumors equal to or greater than 0.75 mm thick. The sentinel lymphnode biopsy is also recommended for thinner tumors that are ulcerated, have lymphovascular invasion or a mitotic rate greater than or equal to 1 mitotic figure per square millimeter. One can use Technetium-99 through a handheld gamma probe for preoperative mapping and intraoperative identification in the operating room. If there is positive identification of a melanoma, authors recommend complete lymph node dissection. Adjuvant interferon alfa is then recommended in patients who have a life expectancy of greater than 10 years. Current Insights On Immunotherapy
      In the past, the prognosis of metastatic melanoma has been poor with a median survival of only 6.2 years and a oneyear life expectancy of 25.5 percent. Currently, immunotherapy with monoclonal antibodies is turning the tide. Therapies that target T lymphocyte antigens can induce an antitumor immune response. Ipilimumab (Yervoy, BristolMyersSquibb) is the first approved immune checkpoint inhibitor and has shown durable objective responses.Twenty percent of patients are now surviving five years with ipilimumab. Complications include exacerbation of preexisting
      immune disorders.Anti-programmed cell death (PD-1) monoclonal antibodies like nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck Oncology) are other immune checkpoint inhibitors that have demonstrated more effective results than conventional drugs in clinical trials for a variety of advanced solid tumors including melanoma, non-small cell lung carcinoma and renal carcinoma. When it comes to plantar melanoma, the five-year disease-free
      survival rates are still significantly worse for patients with plantar melanomas in comparison with leg lesions of the same thickness. The five-year survival rate for plantar melanoma is now 82 percent for lesions up to 1.49 mm and 0 percent for lesions over 3.5 mm.

      In Conclusion
      To help combat the increasing incidence of melanoma, we can improve patient survival with clinical vigilance, improved dermoscopy skills and more biopsies of atypical nevi. After detecting melanoma, referral to a melanoma specific management team will help to improve the melanoma mortality rate.

      Dr. Bodman is an Associate Professor at the Kent State University College of Podiatric Medicine. He is board certified by the American Board of Podiatric Medicine

    • #14271

      Thank you Annette for sharing this. It is quite informative.

    • #14274
      Annette CyrAnnette Cyr

      Glad you found it useful. How are you doing?

    • #14281

      I am good thank you for asking, and you? hope all is good.

      Heading for a skin check again next week but i havent found any changes, so i am sure it will be a good visit.

      I did have an abdominal ultrasound a couple months back to look at the lymph nodes in my abdomen for any signs of activity (i think that is the right wording). They did find a lesion in my liver which freaked me out and a CT scan confirmed a 9 mm lesion. Apparently it isn’t anything to be worried about. Doc is going to repeat ultrasound at end of the year.

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