Melanoma, also known as malignant melanoma, is a highly malignant tumor that occurs mostly in the skin, accounting for the third place (6.8% to 20.0%) of skin malignant tumors, accounting for 3.0% of all tumors. The incidence rate is The average speed of 4.0% to 6.0% is increasing year by year. Among patients who die from cancer, melanoma accounts for about 1.0%. Because of the high degree of malignancy, unclear etiology, complicated pathogenesis, and lack of specific early diagnosis, studies on the etiology and pathogenesis of melanoma have attracted more and more attention from clinicians. Melanoma is derived from melanocytes, which are widely found in the basal layer of the squamous epithelium such as the skin, mouth, part of the nasal cavity and vaginal mucosa, and also in the ectodermal sources such as the uveal, meninges and anal mucosa. In the organization. Melanoma can be evolved from congenital or acquired benign pigments, or it can be new . Non-pigmented melanomas are often overlooked. With melanoma patients with a history of trauma and misdiagnosed patients, the relationship between trauma and melanoma has attracted the attention of scholars at home and abroad. Some scholars believe that the traumatic event of the patient may be a risk factor for the onset of melanoma. The trauma is related to the onset of melanoma, but some scholars believe it is a coincidence. At present, the role of trauma in the pathogenesis of melanoma remains unclear. Whether there is a direct correlation between trauma and melanoma is still controversial. This article reviews the current research progress on the relationship between trauma and melanoma at home and abroad.
1. Clinical manifestations of melanoma after trauma
Post-traumatic melanoma (defined here as melanoma formed at the trauma site after trauma) is frequently reported, suggesting that there may be some association between trauma and melanoma. Jukic et al. and Naseri et al reported that primary corneal melanoma occurred in corneal penetrating lesions and blunt sites; el Baba and Blumenkranz reported that patients with ocular penetrating wounds were found to have glucose melanoma after many years; oral melanin Tumors often occur at the edge of dentures, considering the trauma caused by chronic friction of the dentures as a predisposing factor; there are also reports of submandibular melanoma often occurring after a nail crush or avulsion; skin melanin Tumors can also occur in tattoos and burn scars; acral melanoma often involves penetrating wounds in the hands and feet, repeated compression and grinding of the heel. Post-traumatic melanoma is often characterized by ulcers, nodules and light pigmented lesions. Its clinical manifestations are atypical, and different parts can present different clinical features. Denture-associated melanoma often presents as ulcerative nodules with or without pigmentation. After the extremity trauma, melanoma can be manifested on the basis of with or without melanin, sustained uncement after kick, squeezing and stabbing, or repeated ulceration, ulceration after the wound heals, forming a lump, or healing after trauma The remaining pigmentation spots are enlarged, and some patients have enlarged lymph nodes. Sustained pain and swelling after acute crush injury, and chronic malformation caused by malformation may be a clinical manifestation of melanoma. In addition, destructive bone lesions caused by trauma are sometimes hypothyroidoma or the first clinical manifestation of metastatic melanoma.
2. Epidemiological analysis of trauma and melanoma
2.1 The relationship between trauma and melanoma
Retrospective or controlled studies of the clinical features (morbidity, trauma history, gender, and region) of melanoma patients associated with melanoma support support the risk of trauma associated with melanoma. According to anatomical location, Green et al. counted 1848 patients with cutaneous melanoma, and calculated the average risk of melanoma on the entire body surface and the risk of disease at the corresponding anatomical site by the incidence of melanoma per unit surface area. The risk of melanoma in the back of the foot is three times higher than the mean and eight times higher in the sole. According to Zhang et al., the incidence of melanoma in the extremities is higher than that in other parts of the body. The risk of melanoma after trauma is also significantly higher than other parts. Sun Dongjie et al. and Gao Tianwen count the melanoma patients. After analysis, it was found that: malignant melanoma of the extremity accounted for about 2/3 of the skin melanoma; the main site of the disease was heel, ankle and thumb (toe) under the armor, mostly affected parts, vulnerable to trauma or not easy to detect. Chronic trauma; melanoma patients with a clear history of trauma (such as nail puncture and kick injury) account for about one-fifth of all skin melanomas, 1/3 of acral melanoma . Studies have retrospectively analyzed patients with subcutaneous melanoma in Bologna and Germany, and found that underarm melanoma has the highest incidence of thumb and thumb, while thumb and big toe are the most vulnerable to trauma. The history of trauma was as high as 64.5% in melanoma. Special forms of trauma, such as burns, Cho et al., report a 14-year prospective study that showed a high risk of melanoma in patients with a history of burns, and with the increase in the number of burn scars, the risk of disease increase. The above clinical study data suggest that trauma is associated with the onset of melanoma. Green et al and Rolon et al. used a healthy study and non-melanoma patients as a control group to conduct a controlled study with melanoma patients, indicating that the history of trauma (especially deep penetrating wounds of the hands and feet) is acral melanoma. An important risk factor for high morbidity. Lea reviewed the history of trauma, and used basal cell carcinoma as a control. It was found that the proportion of melanoma patients with trauma was higher than that of the control group, suggesting that trauma is a direct cause of melanoma. Direct malignant changes or the induction and development of melanoma on the basis of pigmented nevus. Studies have shown that trauma is an independent risk factor for melanoma. Repeated trauma can cause a multiplicative effect on the risk of melanoma. Lesage et al believe that there is a “dose-effect” relationship between trauma and melanoma.
2.2 Sex and Melanoma
Melanoma occurs in men, and the ratio of male to female incidence is about 3:2. Cho et al. used multi-class Logistic regression to analyze the effects of melanoma risk factors at different locations. The results showed that men were at higher risk for head, neck and trunk melanoma compared with women. Epidemiological statistical analysis also showed that the history of trauma in men with melanoma was significantly higher than that in women. Because men take more outdoor labor or physical activity in human society, there is a greater risk of exposure to trauma, especially the head, neck and torso. The risk of trauma explains from another perspective that the incidence of melanoma in men is greater than that of women, suggesting that trauma plays an important role in the pathogenesis of melanoma. It is well known that in terms of race and genetics, the incidence of Caucasian melanoma is higher than that of blacks. Norval et al. performed a statistical analysis of the incidence of melanoma in black and white Africans. It was found that although the incidence of black melanoma in African whites is about 20 times that of blacks, the incidence of black lower limbs and hip melanoma is significantly higher than that of whites. It believes that this difference can be explained by the fact that black Africans are more susceptible to trauma due to burns, scars, insect bites and walking barefoot. This suggests that the risk of trauma may affect the incidence of melanoma in different parts of different populations.
3. Mechanisms related to trauma and melanoma
Epidemiological studies have found that trauma is associated with the onset of melanoma, but the specific mechanism of action caused by melanoma in specific trauma has not yet been fully unified. At present, there are several mechanisms in the literature.
3.1 Increased trauma DNA mutation
Biologically, melanoma formation is based on DNA mutations in normal melanocytes. It has been reported in the literature that under high-sensitivity genetic susceptibility conditions, melanocytes undergo a certain number of mitosis, which can cause sufficient mutations to induce tumors; physical trauma or trauma leads to acute or chronic proliferative reactions, accelerate mitosis, accelerate DNA mutation, increase black The risk of developing a tumor.
3.2 Trauma caused by tumor-associated cytokine secretion
The physiological processes of wound healing and the pathological processes of tumorigenesis and development have much in common. At different stages of wound healing, epithelial cells, endothelial cells, and inflammatory cells involved in the healing process can release a variety of effective cytokines for several months, such as vascular endothelial growth factor (VEGF), epidermal growth factor, and leukocyte IL (IL), fibroblast growth factor and transforming growth factor, etc., and some of these factors have been confirmed to participate in tumor growth, creating a microenvironment that is conducive to melanoma. Further studies by Westphal et al have confirmed that VEGF, basic fibroblast growth factor, IL-8, and platelet-derived growth factor AB can promote the proliferation and differentiation of melanocytes or tumor microvessels, which can promote the occurrence and development of melanoma.
3.3 Trauma promotes malignant transformation of melanocytes
Melanoma is derived from the poor differentiation and malignant transformation of melanocytes. Zhou Fengqing and Zhang Sanzhong believe that melanoma most often occurs in the vulnerable parts of the feet, back, waist and head. The occurrence may be caused by foot trauma, infection and stimulation leading to the proliferation of melanocytes in the squamous epithelium of the skin. It is related to malignant transformation. Hussain et al. believe that the link between trauma and melanoma: one may be caused by trauma to induce melanocyte proliferation, mutation during proliferation and differentiation, leading to the formation of melanoma; another possibility may be the formation of scar after trauma In the process of releasing autologous and xenogeneic cells, the release of toxins can promote the malignant transformation of melanocytes. In addition, the entry of traumatic implanted epithelial components into the dermis has also been proposed as a potential mechanism. Under normal circumstances, there is no melanocytes in the cornea. The source of melanocytes of primary corneal melanoma after trauma causes Naseri et al. to emphasize that local inflammation and ischemia after trauma may lead to the formation of melanocytes. The pathway of cell metastasis; at the same time, the corneal nerve cells homologous to neural crest after traumatic stimulation, as well as the corneal basal cells may be the source of potential melanocyte progenitors. At present, most studies on trauma and melanoma are limited to epidemiology. The specific role of trauma in the pathogenesis of melanoma remains unclear. It may promote the mutation and deterioration of melanoma cells by increasing DNA mutations and releasing relevant cytokines. This leads to the formation of melanoma. Due to its atypical clinical manifestations, post-traumatic melanoma is often misdiagnosed as chronic inflammatory lesions, granuloma, squamous cell carcinoma and hemangioma, and even if distant metastases are often misdiagnosed. It has been reported that patients from traumatic events to melanomas are diagnosed for months to years or even decades. Zhou Fengqing and Zhang Sanzhong performed statistical analysis on 10 cases of post-traumatic melanoma in China. The results showed that the time of non-healing ulceration after trauma lasted for about half a year to one year, and ulceration to melanoma inguinal lymphatic metastasis was about 1~2 years. However, due to the atypical clinical manifestations of melanoma, clinically misdiagnosed or missed diagnosis, the exact time from the traumatic event to the occurrence of melanoma cannot be known. In the diagnosis of melanoma, the history of trauma should be given special attention, especially in the case of long-term, long-term non-healing or repeated injury. However, the role of trauma should not be overestimated or exaggerated. Early diagnosis of melanoma remains a challenge for doctors in atypical clinical manifestations and misleading medical history. Therefore, the relationship between trauma and melanoma, the mechanism of action, and the epidemiological characteristics of trauma and melanoma such as clinical manifestations, tumor thickness, histopathological types and prognosis still require further research and exploration.