Acral melanoma was first named by Reed in 1976 [7] and became the fourth melanoma to be listed as a single subtype. The disease has unique clinical and pathological characteristics, such as anatomic structure defined as "acral", including the hands and feet, a pathological type defined as "acral type." Subungual is a particular type of acral melanoma. Acral melanomas account for only 1–7% of cutaneous melanomas in white populations, while 50–58% in Asia populations and up to 60–70% in blacks [8, 9]. Acral melanoma is the most distinctive type of melanoma in China. The incidence sites are mostly in the palm, plantar, heel, toe, interdigital and other places where there were rarely exposed to ultraviolet irradiation, indicating that the incidence has nothing to do with sun exposure [5, 10]. It is characterized by insidious onset, rapid development, easy occurrence of lymph and systemic metastasis with poor prognosis [11].
In the past five years, a total of 357 patients with MM were admitted and treated in our hospital, including 109 cases of acral melanoma on feet, accounting for 30.53% of all melanoma and 75.17% of acral melanoma patients. Clinical data were extracted and summarized from several foreign centers. The results showed that among the patients with AM, the incidence of the foot was about 77.6%, while that of hand was 22.4%, and the prevalence of hand/foot was about 1/3 (see Table 2). These outcomes are consistent with those observed in our hospital. The possible reason justifying that the incidence of the foot is noticeably higher than that of the hand is related to the hidden location of the disease and the high probability of trauma. Female patients were slightly more, accounting for about 52.29%. The patients were mainly middle-aged and elderly, and the onset age was 50–60 years old, with an average age of 58.31 years old. Among them, farmers and other manual laborers accounted for 63.3%. The incidence sites were mainly concentrated on the medial and lateral longitudinal arch of the foot, including the big toe, the medial or lateral sole of the forefoot, the lateral sole and the heel, accounting for about 80% of the incidence sites on foot. Among the causes of the disease, a total of 57 cases, about 52.3% of the patients had malignant nevus. Therefore, moles in the plantar weight-bearing area should be removed to avoid cancerous changes. Secondly, traumatic stimuli [12], such as excision misdiagnosed as "corns" or local ulceration caused by repeated friction, are the main factors to induce malignant tumors. About 40% of patients had "negligence" of the disease.
Table 2
Incidence of acral melanoma happened on hand, foot in different countries or regions.
| Author and year | Country or region | year | total number (location) | Hands (n %) | Foot (n %) |
| Hinds1979 [26] | Hawaii, USA | 1960–1977 | 64 (skin) | 12 (19) | 22 (34) |
| Blessing1991 [27] | The British | 1979–1989 | 100 (extremity) | 52 | 48 |
| Green1993 [28] | Scotland Australia | 1979,1980,1987 | 1848 (skin) | 9 (0.5) | 28 (1.5) |
| Krishnamurthy1994 [29] | India | 1964–1984. | 126 (extremity) | 4 (3.2) | 53 (42.1) |
| Garsaud1998 [30] | The French | 1976–1995. | 72 (extremity) | 3 (3.8) | 39 (3.8) |
| Bulliard2007 [31] | The Swiss | 1995–2002. | 1658 (skin) | 15 (0.9) | 56 (3.4) |
| Bradford2009 [32] | The United States | 1986–2005. | 90298 (skin) | 311 (0.3) | 1102 (1.2) |
| Carrera2017 [33] | The Caucasus | 1986–2010. | 269 (extremity) | 47 (17.5) | 222 (82.5) |
| Total | | | | 453 (22.4) | 1570 (77.6) |
At present, there are problems with the diagnosis and treatment of AM on foot, such as hidden location of disease, lack of knowledge in patients, and improper surgery in some hospitals. The average duration of the disease was 5.92 months in the patients’ first admission in our hospital. Pathology examination showed that the tumor Breslow was 2–7 mm thick, with an average thickness of 4.06 mm, which was similar to a study conducted at Peking University Cancer Hospital (Beijing, China) with 41.8% (218 cases) of AM in 522 MM patients, and tumor thickness greater than 4 mm accounted for 36.7% [13]. The number of postoperative inguinal and iliac fossa lymph node metastases was 1–16, with an average of 3.35. During the first hospitalization, there were 67 patients with definite clinical stages, including 24 patients with stage I, seven patients with stage II, 20 patients with stage III, and 16 patients with stage IV, in which stage III and IV accounted for 33.03% of all patients. The lactate dehydrogenase (LDH) level was increased in 16 cases. Genetic tests showed 5 patients with BRAF V600E mutation and 26 patients without mutation.
In the present research, a total of 80 patients, accounting for 73.4%, were admitted to our hospital after local resection under local anesthesia. The extended resection was performed again in our hospital. Residual tumor was found in 21 cases, and no residual tumor was noted in 32 cases. Tumor recurrence occurred in 8 cases as well. Therefore, unplanned surgery with local anesthesia is one of the significant factors for residual tumor and postoperative recurrence, accounting for 36.25% (29/80) of the patients. The leading causes of residual tumor were as follows: (1) Operators insufficiently understood melanoma and surgical margin was found essential, and were unable to achieve standardized resection; (2) Operators worried about the wound closure and sacrificed the cutting edge. The most important note for unplanned surgery is to clarify the resection margin after an operation. In our department, we are following the highest standard for MM surgery of 2–3 cm outside the tumor border or first cutting edge. Moreover, the depth should include the first operative area and reach beneath the fascia. The enlarged operation did not recur during the follow-up.
Rotated flaps or skin grafts are the main methods of one-stage wound closure after tumor resection on sole [14]. Due to lack of practical adjacent flap of the forefoot, we adopted the sacrifice of the 2nd, 4th, and 5th toes to close the wound through amputation and bone pick flap retention with sensory nerve preserved of the flap, in beneficial of the postoperative weight-bearing walking. The medial and lateral flap on foot can be used to repair the wound of the lateral sole and the posterior heel. When the defect has a diameter larger than 5–7 cm, the sural nerve retrograde flap or the medial leg retrograde flap should be used to repair the wound. At present, there are some disadvantages, such as flap is swollen and lack of sensation. Marginal necrosis is another complication, because of limited blood nourishing the excision of the flap.
Lymph node metastasis is one of the most common features on foot AM. Fujisawa et al. [15] studied the risk factors for lymph node metastasis of AM, including tumor thickness, satellite metastasis or ulceration. In the present research, there were 42 patients with inguinal lymph node swelling at the initial diagnosis. The postoperative pathology confirmed 25 patients with metastasis, accounting for 59.52% of the patients with inguinal (including iliac fossa) lymph node dissection. During the treatment, there were 38 cases of inguinal, popliteal or iliac fossa lymph node enlargement, and 20 cases (52.63%) were confirmed to be positive. Therefore, a total of 43 cases (including 2 patients with recurrence or metastasis of iliac fossa and popliteal fossa) accounted for 39.45% of all AM appeared on foot. After lymph node dissection, the drainage lasted for about 8.75 days on average, and the total drainage volume was 802.86 ml. In the current research, the positive rate of lymph nodes was less than 60%. Low rate of metastasis lymph node may be due to the following reasons: Firstly, swollen lymph nodes were found through preoperative imaging data, including ultrasound and MRI; Secondly, the majority of the patients were admitted to our hospital after surgery from another place. Pathological consultation was unable to detail information, including tumor Breslow thickness, cutting edge, etc. Therefore, clinical staging is intricate, and SLND should be adopted in a number of patients.
There were several complications after inguinal lymph node dissection, which were reported to be 20–40% (mean, 39.3%) [16, 17]. The most common complications included: (1) Postoperative lymphatic leakage and long drainage time (17.9%). The main reason is that the lymphatic vessels were cut off by electrocauterization, and stump of lymphatic vessels partly reopened postoperatively. The clinical presentation is a large quantity of yellow thin exudate. The main preventive measures should be therefore taken: intraoperative careful separation and ligation of the visible lymphatic vessels (e.g., entrance of the femoral canal, inguinal ligament and the area around the fossa ovalis), transfer of sartorius muscle flap to fill the residual cavity, adequate postoperative drainage, appropriate pressure of the wound cavity to promote the adhesion of the remaining cavity fibers, etc. (2) Wound skin necrosis and infection (about 25.4%). The above-mentioned complications can be effectively avoided through the standardized intraoperative operations, such as retaining the appropriate thickness of the subcutaneous fat layer (2–3 mm), subcutaneous tissue separation to prevent the use of electrotome, removing the free skin margin about 1 cm wide before suture, strengthening the dressing change of postoperative wound, and vacuum sealing drainage (VSD). After the occurrence, the wound should be timely treated with dressing change and debridement. For the patients with a large area of necrosis and difficulty in suture, the thigh lateral muscle flap or rectus femoris myocutaneous flap was adopted in our hospital to repair the wound surface. (3) Postoperative limb edema (about 20.9%). Some of the symptoms can be alleviated by lifting the affected limb, using stretch socks, and taking anti-swelling drugs orally. However, there is no effective treatment for severe edema.
The adjuvant therapy for the melanoma of the foot in our hospital was mainly high-dose interferon and chemotherapy. Dacarbazine (DTIC) has been recognized as the only chemotherapy drug approved by the Food and Drug Administration (FDA) for progressive MM since 1972 [18]. In recent years, with the development of genetic testing technology, exploration of immune- and targeted-therapy, immune therapy has been gradually used for these patients [20, 21]. Clinical studies showed that the skin melanoma with more mutated BRAF gene mutation and AM accounted for only 17% of BRAF gene mutations, and KIT gene mutation was 15% ~ 40% (3, 22). Additionally, the efficacy of nivolumab in melanoma has been recognized [21]. However, there is still lack of objective data to evaluate AM patients in China, thus, the efficacy of targeted therapy and immunotherapy needs to be studied for a long period of time.
It has been reported [13, 23, 24] that the main factors affecting the prognosis and survival of patients are the clinical stage of the tumor, lymph node metastasis, and metastasis of vital organs. Others include lactate dehydrogenase, BRAF gene mutation, etc. A Chinese study confirmed that factors, such as ulcer, tumor resection margin, and lymph node metastasis are the main factors influencing the prognosis of MM patients, and immunotherapy may improve the median survival of patients [25]. In the majority of AM patients, independent factors affecting the prognosis were as follows: duration of damage before diagnosis (2.5 years) or less, Breslow thickness > 4.0 mm (grade 4 primary focal T stage), high mitotic index (> 15 mm), vascular invasion and regional lymph node metastasis, and pathological staging (Ⅱ/Ⅲ/Ⅳ) [5]. The present study unveiled that the occupation of patients was one of the significant factors in the occurrence of tumor-related events. It was noted that our patients were mainly manual laborers, with lack of medical knowledge, delayed detection, irregular treatment, which led to postoperative tumor recurrence, lymph node metastasis, and other related events. The specific site of tumor growth is one of the factors that affects the survival of patients. Different parts of the plantar have different effects on patients' loading and walking, resulting in different lengths of disease, which may be the cause of tumor metastasis and death. In the multivariate regression analysis, no prognostic indicators were found. The results may be related to the retrospective study of this group of patients, a limited number of patients, incomplete clinical and follow-up data (e.g., incomplete preoperative imaging data and irregular pathological reports), a small number of cases reaching the observation endpoint and other factors. Therefore, the next study should expand the sample size, standardize the clinical and pathological diagnosis and treatment process, involving further research indicators, and extend the postoperative follow-up time to obtain more effective tumor prognostic indicators.
Shortly, foot melanoma is a kind of aromatic melanoma. Its features include high incidence in farmers and other manual workers, the leading site of the plantar weight-bearing area, easily misdiagnosing and mistreating tumor, high lymph node and organ metastasis rate. At present, the primary treatment is surgery, postoperative adjuvant chemotherapy, and biological therapy, while the prognosis is relatively poor. Preventive resection of precancerous lesions and early diagnosis and treatment of tumors are the primary tasks to improve the efficacy and survival of patients.