Abstract：
Spitz tumors are a subset of melanocytic neoplasms characterized by epithelioid or spindled melanocytes(1). The benign nature of the \"Spitz nevus\" has since been clarified, but the debate regarding Spitzoidtumors (STs) is still ongoing. Spitzoid tumors encompass a wide spectrum of cutaneous lesions ranging from benign Spitz nevus (SN) to Spitzoid melanoma (SM), the latter displaying capacity for widespread metastasis and a potentially lethal outcome (2). The term atypical Spitz tumors (ASTs) refers to melanocytic tumors exhibiting the morphological features of SN, as well as some features associated with malignancy, but not sufficient to classify them as SMs. Currently, histopathology is the gold standard for the diagnosis of STs and cutaneous MM. However, the differential diagnosis between benign and malignant melanocytic lesions with spitzoid features remains challenging (3-6). In order to facilitate the work of clinicians and pathologists, we attempted a comparative clinical and demographic study comparing ASTs and MMs of patients referred to two Italian institutes. Patient data were obtained from two different Italian dermatological centers (Melanoma Registry of the Instituto Dermopaticodell\'Immacolata IDI-IRCCS Rome, Lazio and the Skin Cancer Unit of Dermatology, Hospital Sant\'Orsola-Malpighi, University of Bologna), from January 2007 to December 2017. Histological reports presenting pre-operative queries of both \"atypical Spitz nevi\" or \"malignant melanoma\" and a final diagnosis confirming one of the queries were included in the study. The chi-square test or Mann-Whitney U-test were applied to analyze differences between the groups for categorical variables such as sex, diagnosis, and continuous variables (age). The \"anatomic site\" variable was classified into three categories as follows: the limbs, trunk, and head/neck. A multivariate binary logistic model was used to investigate if the anatomic site was an independent predictor of MM. Age and sex were considered confounding factors. A total of 504 patients (51.8% men; 48.2% women) met the inclusion study criteria (mean age 52 years, SD = 22.8) (Table 1). 373 were cases of MM and 131 were cases of AST. Mean age of MM cases and AST were 61.2 years old (SD = 17.6) and 25.8 years old (SD = 13.8), respectively. Subjects with MM were predominantly men (58.2% versus 33.6%) (P<0.0001) and older (median age 62 years versus 25 years) (P=0.0001) than subjects with AST. The most frequent anatomic site for MM was the trunk (39.7 %), while the lower limb was the most frequent anatomic site for AST (48.1 %) (P<0.0001). Table 2 shows the multivariable analysis used to assess if anatomic site was an independent predictor of cutaneous melanoma. Multivariate analysis confirmed an increased risk for MM in comparison with AST for both localization on the trunk (OR:2.78; 95 %CI: 1.74-4.45) (P<0.0001) and head/neck (OR:3.20; 95% CI: 1.60-6.38) (P=0.0001). After introducing age (model 1, OR: 2.11; 95% CI: 1.08-4.12) (P=0.003) and sex into the model, the only anatomic site that remained statistically significant was the trunk (model 2, OR: 2.03; 95% CI: 1.0.3-3.99) (P=0.04). The results show that if the lesion was located on the trunk, the probability of being a MM was two times higher than that of AST, independent of sex, age, or center. After stratifying for sex, the effect was stronger for women (OR: 2.72; 95% CI: 1.14-6.50). After stratifying for age, the effect was stronger for younger subjects (<40 years) (OR: 2. 59; 95% CI: 1.20-5.60) (P=0.02). In this study, we focused on the clinical-epidemiological data in an attempt to improve the identification of nodular melanocytic lesions by providing clinicians with further information in order to reduce the rate of misdiagnosis and assist in providing critical clinical information to surgeons and pathologists. Consistently with the literature, ASTs were mainly found in young-adult patients (mean age was 25.8 years), in the female sex (66.4%), and were typically located on the lower limbs (48.1%) (3,7-10). MM were found to be slightly more common in male patients (58.2%) in the overall patient group; the mean age at the time of the diagnosis was 61.2 years old, and the majority of lesions were located on the trunk (39.7%). These data were similar to those reported by other authors (11-13). ASTs cases were mainly women and younger than MM cases, and were typically located on the lower limbs (Figure 3 and Figure 4). Nodules located on the trunk resulted in a two times greater risk of MM in comparison with AST. In summary, distinguishing ASTs from MMs is often challenging, and histopathology remains the diagnostic gold standard for melanocytic neoplasms, but a specific clinical framework may help surgeons, pathologists, and clinicians to correctly diagnose and manage these lesions in children and adults.
摘要：
Spitz肿瘤是以上皮样黑素细胞或纺锤形黑素细胞为特征的黑素细胞肿瘤的子集(1)。此后，“斯皮茨痣”的良性性质得到了澄清，但是关于Spitzoidtoma（STs）的争论仍在进行中。Spitzoid肿瘤涵盖广泛的皮肤病变，从良性Spitz痣（SN）到Spitzoid黑色素瘤（SM），后者表现出广泛转移的能力和潜在的致命结果（2）。术语非典型Spitz肿瘤（AST）是指表现出SN的形态学特征的黑素细胞肿瘤，以及一些与恶性肿瘤相关的特征，但不足以将它们归类为SM。目前，组织病理学是诊断STs和皮肤MM的金标准。然而,良性和恶性黑素细胞性病变与皮囊样特征的鉴别诊断仍具有挑战性(3-6).为了方便临床医生和病理学家的工作，我们尝试了一项比较临床和人口统计学研究,比较转诊到意大利两家机构的患者的ASTs和MMs.患者数据来自两个不同的意大利皮肤病学中心（ImmacolataIDI-IRCCS罗马Dermopaticodell研究所的黑色素瘤注册，拉齐奥和皮肤科皮肤癌,Sant\'Orsola-Malpighi医院,博洛尼亚大学），从2007年1月到2017年12月。组织学报告显示了“非典型Spitz痣”或“恶性黑色素瘤”的术前查询，并确认了其中一个查询的最终诊断。卡方检验或Mann-WhitneyU检验用于分析组间分类变量的差异，例如性别，诊断,和连续变量(年龄)。“解剖部位”变量分为以下三类：四肢，树干,和头部/颈部。使用多元二元逻辑模型来研究解剖部位是否是MM的独立预测因子。年龄和性别被认为是混杂因素。共有504名患者（男性占51.8%，女性占48.2%）符合纳入研究标准（平均年龄52岁，SD=22.8)(表1)。MM为373例，AST为131例。MM病例和AST的平均年龄分别为61.2岁（SD=17.6）和25.8岁（SD=13.8），分别。患有MM的受试者主要是男性(58.2%对33.6%)(P<0.0001)和年龄大于AST的受试者(中位年龄62岁对25岁)(P=0.0001)。MM最常见的解剖部位是躯干（39.7％），而下肢是AST最常见的解剖部位（48.1％）（P<0.0001）。表2显示了用于评估解剖部位是否是皮肤黑素瘤的独立预测因子的多变量分析。多变量分析证实，与AST相比，在躯干（OR：2.78;95CI：1.74-4.45）（P<0.0001）和头颈部（OR：3.20;95％CI：1.60-6.38）（P=0.0001）的定位均增加了MM的风险。将年龄（模型1，OR：2.11；95％CI：1.08-4.12）（P=0.003）和性别引入模型后，唯一具有统计学意义的解剖部位是躯干(模型2,OR:2.03;95%CI:1.0.3-3.99)(P=0.04).结果表明，如果病变位于躯干上，成为MM的概率是AST的两倍，与性无关,年龄,或中心。在性别分层后，女性的效果更强(OR:2.72;95%CI:1.14-6.50)。在对年龄进行分层后，年轻受试者（<40岁）的效果更强（OR：2。59；95%CI：1.20-5.60）（P=0.02）。在这项研究中,我们专注于临床流行病学数据,试图通过向临床医生提供进一步的信息来改善结节性黑素细胞病变的识别,以减少误诊率,并协助向外科医生和病理学家提供关键的临床信息.与文献一致，ASTs主要见于年轻成人患者(平均年龄为25.8岁)，女性（66.4%），通常位于下肢（48.1％）（3,7-10）。在整个患者组中，MM在男性患者中更为常见（58.2％）；诊断时的平均年龄为61.2岁，大多数病变位于躯干（39.7%）。这些数据与其他作者报道的数据相似(11-13)。ASTs病例主要为女性，年龄小于MM病例，通常位于下肢（图3和图4）。与AST相比，位于躯干上的结节导致MM的风险高两倍。总之,区分AST和MMs通常是具有挑战性的，组织病理学仍是诊断黑素细胞肿瘤的金标准,但是一个特定的临床框架可以帮助外科医生，病理学家,和临床医生在儿童和成人中正确诊断和管理这些病变。
