Mott Ryan T, Smoller Bruce R, Morgan Michael B
Department of Pathology, University of South Florida College of Medicine, Tampa, FL, USA.
J Cutan Pathol. 2004 Mar;31(3):217-23. doi: 10.1111/j.0303-6987.2004.00149.x.
Merkel cell carcinoma (MCC) is a frequently aggressive neuroendocrine malignancy of the skin that presents in sun-exposed areas on elderly patients. Although originally described over 30 years ago, many aspects of MCC remain to be defined. Of particular importance is the need to identify prognostic factors capable of predicting the biological behavior of these tumors. Knowledge of these factors may help in determining which patients require more aggressive treatment regimens. In this study, we examined 25 cases of MCC with an attempt to identify clinical, histopathological, or immunohistochemical features capable of predicting disease outcome.
Features that we evaluated in each case included age, gender, race, tumor location, tumor size, depth of invasion, growth pattern, lymphocytic infiltration, mitotic activity, ulceration, necrosis, vascular invasion, and perineural invasion. In addition, we examined neural cell adhesion molecule and cytokeratin-20 expression using immunohistochemical methods.
We found that most patients were males (84%) with an average age of 74 years. The tumors were located on the head and neck (68%) and upper extremities (32%). Overall, 64% of the patients developed metastatic disease to regional lymph nodes or distant sites (average follow-up time of 21 months). Local recurrence was also common, occurring in 29% of the patients. The overall 1- and 2-year survival rates were 80 and 53%, respectively. Histopathological examination revealed tumors with an average size of 7.2 mm. Common features included invasion into the subcutaneous adipose tissue, solid growth pattern, tumor necrosis, and vascular and perineural invasion. Findings that had a statistically significant correlation with poor outcome included tumor size > or =5 mm (p = 0.047), invasion into the subcutaneous adipose tissue (p = 0.005), diffuse growth pattern (p = 0.040), and heavy lymphocytic infiltration (p = 0.017). The remaining findings, including the immunohistochemical results, did not correlate with disease outcome. Using logistic regression models, we show that depth of invasion and degree of lymphocytic infiltration are strong predictors of disease outcome.
The current controversies regarding the treatment of early-stage MCC (i.e., localized disease) underscore the importance of identifying clinicopathological features capable of predicting tumor behavior. In this study, we have identified several prognostic features in MCC. Perhaps, these features may prove useful in identifying patients who require more aggressive treatment regimens.
默克尔细胞癌（MCC）是一种常见的侵袭性皮肤神经内分泌恶性肿瘤，好发于老年患者阳光暴露部位。尽管早在30多年前就有描述，但MCC的许多方面仍有待明确。特别重要的是，需要确定能够预测这些肿瘤生物学行为的预后因素。了解这些因素可能有助于确定哪些患者需要更积极的治疗方案。在本研究中，我们检查了25例MCC病例，试图确定能够预测疾病转归的临床、组织病理学或免疫组化特征。
我们在每个病例中评估的特征包括年龄、性别、种族、肿瘤位置、肿瘤大小、浸润深度、生长方式、淋巴细胞浸润、有丝分裂活性、溃疡、坏死、血管浸润和神经周围浸润。此外，我们采用免疫组化方法检测神经细胞黏附分子和细胞角蛋白-20的表达。
我们发现大多数患者为男性（84%），平均年龄74岁。肿瘤位于头颈部（68%）和上肢（32%）。总体而言，64%的患者发生区域淋巴结或远处转移（平均随访时间21个月）。局部复发也很常见，29%的患者出现局部复发。1年和2年总生存率分别为80%和53%。组织病理学检查显示肿瘤平均大小为7.2 mm。常见特征包括侵犯皮下脂肪组织、实性生长方式、肿瘤坏死以及血管和神经周围浸润。与预后不良有统计学显著相关性的发现包括肿瘤大小≥5 mm（p = 0.047）、侵犯皮下脂肪组织（p = 0.005）、弥漫性生长方式（p = 0.040）和大量淋巴细胞浸润（p = 0.017）。其余发现，包括免疫组化结果，与疾病转归无关。使用逻辑回归模型，我们表明浸润深度和淋巴细胞浸润程度是疾病转归的有力预测指标。
目前关于早期MCC（即局限性疾病）治疗的争议凸显了确定能够预测肿瘤行为的临床病理特征的重要性。在本研究中，我们已经确定了MCC的几个预后特征。也许，这些特征可能有助于识别需要更积极治疗方案的患者。
