儿童黑素瘤临床研究进展

儿童黑素瘤较为罕见, 不同亚型的肿瘤存在发病机制的差异。部分肿瘤临床表现并不典型, 成人黑素瘤诊断标准可能不完全适用于儿童。手术是一线治疗手段, 具体切缘范围可小于成人。近年来黑素瘤的免疫治疗、靶向治疗等治疗手段迅速发展, 但相关药物很少获批儿童适应证。儿童黑素瘤治疗的大样本研究也较少, 但有文献报道相关药物的应用。本文综述儿童黑素瘤发病机制、临床表现和治疗的相关进展, 以期为儿童黑素瘤的诊治提供参考。     

205 Spitz痣

1948年Spitz第一次发表了儿童的一种特殊损害的诊断标志,尽管它有时组织学上很象恶性黑素瘤,但确信它是一种良性病变,Spitz提议对这一疾病用“良性幼年黑素瘤(Benign Juvenile melanoma)”的病名。     

无黑素性恶性黑素瘤1例

恶性黑素瘤(MM)是一种高度恶性的肿瘤,多发生于皮肤,占皮肤恶性肿瘤的6.8%～20%,好发于30岁以上的成年和老年人,儿童罕见.恶性黑素瘤的类型较多,临床表现亦各异.现将作者所见到的1例报告如下.     

黑素瘤细胞中脂肪酸结合蛋白7的表达及其与细胞增殖、凋亡的关系

目的探讨黑素瘤细胞中脂肪酸结合蛋白7(FABP7)的表达及其与细胞增殖、凋亡的关系。方法采用免疫组织化学方法分析临床45例良性痣(为皮内痣)、60例原位黑素瘤、60例转移性黑素瘤标本中FABP7的表达。取组织细胞进行体外培养,选择FABP7特异性小干扰RNA(siRNA)降低FABP7的表达,然后检测黑素瘤细胞的增殖及凋亡情况。结果良性痣细胞浆及细胞核中FABP7的表达均高于原位黑素瘤、转移性黑素瘤(P<0.05),原位黑素瘤和转移性黑素瘤细胞浆及细胞核中的FABP7表达差异无显著性(P>0.05)。下调FABP7表达可减少原位黑素瘤细胞31.0%及转移性黑素瘤细胞81.0%的增殖性,下调FABP7表达对原位黑素瘤及转移性黑素瘤细胞的凋亡率无明显影响。结论良性痣中FABP7表达比黑素瘤高,FABP7对体外培养黑素瘤细胞增殖有影响。     

黑素瘤抑制性活性蛋白及基质金属蛋白酶－9在恶性黑素瘤的表达

目的：探讨黑素瘤抑制性活性蛋白（MIA）及基质金属蛋白酶-9（MMP-9）在恶性黑素瘤中的表达以及作用。方法：应用SP免疫组化技术对38例恶性黑素瘤石蜡标本以及32例色素痣石蜡标本检测MIA及MMP-9表达水平。结果：MIA在所有色素痣中表达阴性,而在原位黑素瘤、侵袭性黑素瘤、有淋巴结转移恶性黑素瘤、无淋巴结转移恶性黑素瘤阳性表达率分别为21.4%,91.6%、94.1%、42.8%,MMP-9在恶性黑素瘤阳性表达率为71.1%,MIA的表达与MMP-9的表达呈正相关。结论：MIA在恶性黑素瘤的发生发展中起着重要作用,这种作用可能是通过上调MMP-9的表达来实现的。MIA有可能成为临床诊断、治疗恶性黑素瘤的有力靶点。     

恶性黑素瘤的端粒酶活性研究

目的检测恶性黑素瘤标本中的端粒酶活性,探讨端粒酶在黑素瘤发生机制中的作用。方法采用聚合酶链反应-酶联免疫吸附测定法(PCR-ELISA),对黑素瘤标本进行端粒酶的定性和定量分析。结果90.0％的原发性黑素瘤和100％的转移性黑素瘤显示端粒酶阳性,仅14.3％的黑素细胞痣呈阳性,而正常皮肤中均为阴性。转移性黑素瘤、原发性黑素瘤、黑素细胞痣和正常皮肤的端粒酶活性水平的平均A值分别为0.729、0.405、0.118和0.044。各组端粒酶活性A值之间经统计学分析差异有显著性。结论大部分恶性黑素瘤患者中存在高水平的端粒酶活性,提示端粒酶可能在黑素瘤的发生机制中起重要作用,对黑素瘤的诊断有一定的临床意义。     

少见病理类型的恶性黑素瘤

恶性黑素瘤是一种高度恶性的肿瘤,多发生于皮肤。根据恶性黑素瘤的临床及病理特点,通常将恶性黑素瘤分为原位恶性黑素瘤(malignant melanoma insitu)和侵袭性恶性黑素瘤(invasive malignant melanoma)。原位恶性黑素瘤又分3型,分别为恶性雀斑样痣(lentigo maligna)、浅表扩散性原位恶性黑素瘤(superficial spreading malignant melanoma)及肢端原位恶性黑素瘤(acral melanoma in situ)。     

恶性黑素瘤与黑素干细胞

恶性黑素瘤是高度转移性肿瘤,对传统的治疗抵抗,黑素瘤的发生涉及遗传和环境因素。大多数黑素瘤为原发性,但部分黑素瘤从黑素细胞痣发展而来。以往认为,长期暴露于紫外线、皮肤黑素细胞逐渐积累致癌基因、肿瘤抑制基因发生突变导致了黑素细胞的增殖,并获得侵袭性和转移的能力,成为黑素瘤。另有假说认为,黑素瘤起源于毛囊外真皮黑素干细胞,紫外线诱导的突变可能会改变正常黑素干细胞自我更新、扩展和分化的过程,导致黑素瘤的形成。深入了解黑素瘤的发生机制,有利于寻求更好的治疗方案。     

黑素瘤抗原疫苗的研发进展

黑素瘤恶性程度高、侵袭性强、治疗棘手、预后差。随着免疫学的发展及对黑素瘤发生发展机制的进一步认识,黑素瘤抗原疫苗已成为黑素瘤治疗的热点。黑素瘤抗原疫苗通过主动免疫放大黑素瘤患者体内抗肿瘤免疫应答,具有特异性强、耐受性低等优点。本文主要对黑素瘤抗原疫苗分类、作用特点、研发进展现状及佐剂作一综述。     

5例少见恶性黑素瘤的临床和组织病理分析

一些特殊类型的黑素瘤因临床和组织病理表现不典型,很容易误诊。该文报道5例少见恶性黑素瘤患者的临床和组织病理特点。其中无色素性黑素瘤2例,肢端黑素瘤局部转移、皮赘状先天性色痣恶变、结缔组织增生性和向神经性黑素瘤各1例。     

Reed nevus (pigmented spindle-cell nevus): a report of three cases with distinct dermoscopic patterns

Reed nevus or pigmented spindle-cell nevus may mimic cutaneous melanoma; however, its dermoscopic and histopathological characteristics are different. This case report describes three patients with distinct clinical, dermoscopic and histopathological presentations, which were correlated to enable a differential diagnosis to be made between melanoma and Spitz nevus.     

Detection of alpha- and beta-human papillomavirus (HPV) in cutaneous melanoma: a matched and controlled study using specific multiplex PCR combined with DNA microarray primer extension

Abstract:  There are few contradictory studies investigating the involvement of HPV in melanoma. We designed a controlled study to evaluate the HPV DNA prevalence in melanoma. One hundred patients with cutaneous malignant melanoma diagnosed between 2002 and 2006 were included. Complementary wide excision (healthy skin) was performed in 85 patients and was used as internal control. After DNA extraction, 68 different HPV types were studied using a multiplex PCR combined with microarray primer extension. We did not observe any statistical significant difference in terms of HPV DNA prevalence in melanoma (38.8%) and in healthy skin from wide excision (42.4%). Twenty-one different HPV types were detected but only one type was present in the majority of our samples (80/85 melanoma vs 59/66 HS). The distribution of HPV genera and types was similar in melanoma and HS, and beta-HPV was predominant (30.6% and 31.8%). Among alpha-HPV (10.6%), high-risk mucosal HPV16 was predominant. Among beta-HPV, melanoma harboured significantly more type 22 than control normal skin from the same patients and significantly less type 21 than paired control normal skin. No correlation between clinical and pathological melanoma characteristics and HPV DNA prevalence was found. Our data do not support a role of HPV infection in melanocarcinogenesis, but confirm the previous data suggesting that HPV DNA is widely distributed among the population and that occult HPV infections are frequent. Furthermore, specific HPV types, such as a-HPV16 and beta-HPV species 2 may be involved in a sub-group of melanoma.     

外伤相关黑素瘤87例临床病理特点与预后分析

目的:分析外伤相关黑素瘤的临床病理特点及其与患者预后间的关系。方法:回顾性分析2009—2020年第四军医大学西京皮肤医院87例外伤相关黑素瘤的临床病理特点,通过Mann-Whitney检验分析不同年龄、性别患者间肿瘤Breslow厚度的差异;通过Spearman秩相关分析外伤至发现皮疹的时间与Breslow厚度之间的...     

Melanoma asociado a nevo melanocítico

The association of melanoma with a preexisting melanocytic nevus varies considerably between series, depending on whether the association is based on histological signs (4%-72%) or a clinically evident lesion (42%-85%). Histological association with a nevus correlates with favorable prognostic factors, whereas a clinical association correlates with unfavorable factors. In this review, we discuss the characteristics of nevus-associated melanoma from different perspectives: Whiteman's divergent pathway hypothesis for the development of cutaneous melanoma; and the factors involved in nevogenicity, including both the genetic and molecular factors involved in the development of the melanoma and its precursor lesions. Finally, a cumulative analysis of the 16 162 cases reported in the literature revealed that 29.8% of melanomas are histologically associated with a melanocytic nevus.     

Extraction of skin lesion texture features based on independent component analysis

Background/purpose: During the recent years, many diagnostic methods have been proposed aiming at early detection of malignant melanoma. The texture of skin lesions is an important feature to differentiate melanoma from other types of lesions, and different techniques have been designed to quantify this feature. In this paper, we discuss a new approach based on independent component analysis (ICA) for extraction of texture features of skin lesions in clinical images.
Methods: After preprocessing and segmentation of the images, features that describe the texture of lesions and show high discriminative characteristics are extracted using ICA, and then these features, along with the color features of the lesions, are used to construct a classification module based on support vector machines for the recognition of malignant melanoma vs. benign nevus.
Results: Experimental results showed that combining melanoma and nevus color features with proposed ICA-based texture features led to a classification accuracy of 88.7%.
Conclusion: ICA can be used as an effective tool for quantifying the texture of lesions.     

AgNOR (nucleolar organizer regions) staining in malignant melanoma.

Nucleolar organizer regions (NORs) are loops of ribosomal DNA seen in nuclei, which are demonstrable as black dots (AgNOR) in tissue sections by silver (Ag) colloid staining. The number of such AgNORs is correlated with cellular activity and is an indicator of the degree of malignancy. In this study, 76 melanocytic lesions were analyzed by AgNOR staining, and the clinical and histopathological characteristics of malignant melanoma and melanocytic nevi were considered. Although the AgNOR counts for melanocytic nevi were significantly different from those in malignant melanoma, an obvious overlap between them was detected. The number of AgNORs in melanocytic nevi per cell was usually 1 or 2. On the other hand, the number of AgNORs per malignant melanoma cell was variable. Morphologically, malignant melanoma cells often showed dispersal of AgNORs throughout the nucleus as well as multiple nucleoli containing clustered AgNORs, whereas melanocytic nevus cells tended to have a regular nucleolus with tightly clustered AgNORs. The correlation between AgNOR count and pathological staging was uncertain, but a slight correlation between AgNOR count and thickness of the primary lesion was obtained. However, the AgNOR count in malignant melanoma was not a prognostic factor for the disease. Therefore, the AgNOR method is difficult to use for differential diagnosis between benign pigmented lesions and malignant melanoma. Nonetheless, an AgNOR count of more than two per cell favors a diagnosis of malignant melanoma.     

Clinical and epidemiological profile of cutaneous malignant melanomas in two referral institutions in the city of Manaus, Brazil

Knowledge on the frequency and clinical and pathological characteristics of cutaneous melanoma in the different geographical regions of Brazil is important in evaluating the magnitude of the problem and in directing healthcare actions appropriately. The present study reviewed data from 55 cases of cutaneous melanoma in patients treated at two healthcare institutions in the city of Manaus, Amazonas, Brazil. Rates were higher in brown-skinned males and in individuals of 70-80 years of age. Lesions were most commonly located on the lower limbs, were of the acral lentiginous melanoma type and at advanced stages of the disease, with Breslow thickness > 1 mm and Clark level V.     

A retrospective study addressed to understanding what predicts severe histological dysplasia/early melanoma in excised atypical melanocytic lesions

BACKGROUND: Atypical naevi are common benign skin lesions but are also recognized both as precursors of and risk factors for melanoma. It is therefore imperative to excise those lesions that are either likely to progress or are already progressing to melanoma. Clinically, however, it may be difficult to distinguish these from benign atypical naevi with bland histology. OBJECTIVES: To analyse the clinical characteristics of excised melanocytic lesions and to identify the predictors of severe histological atypia/melanoma in situ and invasive melanoma. METHODS: The case notes of 434 patients who had melanocytic lesions removed at a pigmented lesion clinic were studied retrospectively. A single pathologist reviewed the excised lesions and clinical characteristics predictive of malignancy were identified. RESULTS: The best predictors of melanoma were older age, history of change and site on an extremity, but only older age was predictive of severe histological atypia/melanoma in situ as opposed to mild to moderate atypical histology. CONCLUSIONS: These results confirm the difficulty of differentiating accurately between benign atypical naevi and borderline lesions or early melanoma in a clinical setting. It is therefore necessary to have a sufficiently low threshold for excision to avoid missing early melanomas, particularly in older patients presenting with lesions on the extremities.     

Comparison of nonfamilial and familial melanoma.

There has been concern that individuals with nonfamilial melanoma and dysplastic melanocytic nevi (DMN) are not directly comparable to patients with hereditary melanoma and DMN. Because we have conducted a comprehensive study of nonfamilial melanoma over the past several years, we have addressed the above issue by directly comparing the characteristics of 145 nonfamilial patients, 6 patients with familial melanoma and the information available for familial melanoma in the literature. All 6 patients with familial melanoma had at least one first-degree blood relative with cutaneous melanoma. A large number of clinical and histologic variables were compared for both groups. Some pertinent variables included mean age at melanoma diagnosis 46.7 versus 52.3 years, mean Breslow thickness 2.11 versus 1.54 mm, mean total body nevi per patient 20.6 versus 18.3, mean total clinically atypical nevi per patient 2.0 versus 1.7 and total histologically confirmed DMN per group 22 (18.3%) versus 2 (33%), for patients with nonfamilial versus familial melanoma, respectively. No substantial differences were observed between the two groups. A review of the medical literature failed to reveal any quantitative data for melanocytic nevi, either clinical or histologic, at present that would allow distinction of patients with sporadic versus familial melanoma. We conclude that studies concerning the clinical characteristics of patients with DMN and nonfamilial melanoma are relevant to other persons with DMN including familial melanoma.     

Smoking,sun exposure,number of nevi and previous neoplasias are risk factors for melanoma in older patients (60 years and over)

Background Malignant melanoma risk factors have been studied in different geographical area populations. However, no study has focused on risk factors which are more frequently associated to the over 60's age group. Methods A case‐control study was performed that included 160 patients age ≥ 60 years diagnosed of cutaneous melanoma and 318 controls matched for age and sex. Both groups were assessed, by personal interview and physical examination, for different phenotype characteristics (hair and eye color, phototype), the presence of other cutaneous lesions (solar lentigines, actinic keratoses and nevi), degree and type of solar exposure and personal and family past history of cutaneous or non‐cutaneous cancer. Differences were evaluated by contingency tables and univariate and multivariate logistic regression. Results Of 17 factors, those risk factors with a strong effect on the development of melanoma in the elderly were: fair eyes, severe sunburns, years of occupational sun exposure, smoking, > 50 melanocytic nevi and personal history of NMSC and other non‐cutaneous neoplasias. Conclusions Tobacco smoking is an independent risk factor for cutaneous melanoma in the elderly. Intense (both acute and chronic) sun exposure and constitutional features, such as tumor susceptibility (NMSC, non‐cutaneous neoplasias, and multiple nevi) are also associated with melanoma risk. All these factors should help to better design educational campaigns in older people.