Wnt/beta-catenin激活的非柔毛皮肤癌:一个病例系列。

IF 7.1 1区 医学 Q1 PATHOLOGY
Thibault Kervarrec , Kuan Cheok Lei , Pierre Sohier , Nicolas Macagno , Marie-Laure Jullie , Eric Frouin , Keisuke Goto , Kohei Taniguchi , Aymeric Hamard , Antoine Taillandier , Anne Tallet , Christine Bonenfant , Yusuf Sahin , Fatoumata Barry , Saleem Taibjee , Kristof Cokelaere , Roland Houben , David Schrama , Charlee Nardin , Francois Aubin , Serge Guyétan
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引用次数: 0

摘要

据报道,在皮肤上皮肿瘤中,APC/CTNNB1 基因的复发性突变会导致 Wnt/β-catenin 通路的激活,这种突变主要发生在母细胞分化的肿瘤中。在本研究中,我们描述了 16 例携带 Wnt/β-catenin 通路激活突变但无成熟分化证据的原发性皮肤癌的形态学、免疫组化和遗传学特征,以及 4 例合并肿瘤,其中类似的 Wnt/β-catenin 激活癌成分与梅克尔细胞癌或柔毛细胞癌相关。在纯肿瘤病例中,6/16 的患者为女性,中位年龄为 80 岁(范围:58-98 岁)。肿瘤位于头颈部(7 例,占 44%)、上肢(4 例,占 25%)、躯干(3 例,占 18%)和腿部(2 例,占 13%)。4例病例出现转移扩散,导致一名患者因病死亡。显微镜下观察,所有病例均为浸润真皮和/或皮下组织的分化不良肿瘤。在 13 个病例中,实性 "鳞状 "区域伴有嗜碱性成分,其特征是玫瑰花瓣/假腺形成,从而形成双相外观。三例标本仅由分化较差的癌组成,缺乏玫瑰花簇形成。免疫组化研究显示,EMA(100%)、BerEP4(100%)、细胞角蛋白7(94%)、嗜铬粒蛋白A(44%)、突触素(82%)和细胞角蛋白20(69%)频繁表达。除一个病例外,所有病例都观察到 Rb 表达的完全丧失。所有病例均检测到核β-catenin和CDX2表达。在 APC(60%)、CTNNB1(40%)和 RB1(n=47%)中观察到复发性致病体细胞突变。全局甲基化分析证实,有玫瑰簇形成的病例构成了一个同质的肿瘤组,有别于已确定的皮肤肿瘤实体(柔瘤癌、梅克尔细胞癌和鳞状细胞癌),而缺乏此类形态特征的其他 3 个病例则没有。此外,我们还发现了 4 例合并肿瘤,其中有一个部分显示出类似的分化不良的莲座状癌,表现出 Rb 缺失和 beta 连环素激活,与梅克尔细胞癌(3 例)或绒毛膜癌(1 例)有关。总之,我们描述了一种独特的肿瘤,并提出了 "Wnt/β-catenin 激活的玫瑰花瓣形成癌 "这一术语,其形态特征是玫瑰花瓣形成、鳞状和/或神经内分泌分化、CDX2 弥漫表达、Rb 缺失以及 CTNNB1/APC 基因突变。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Wnt/β-Catenin–Activated Nonpilomatrical Carcinoma of the Skin: A Case Series

Among skin epithelial tumors, recurrent mutations in the APC/CTNNB1 genes resulting in activation of the Wnt/β-catenin pathway have been reported predominantly in neoplasms with matrical differentiation. In the present study, we describe the morphologic, immunohistochemical, and genetic features of 16 primary cutaneous carcinomas harboring mutations activating the Wnt/β-catenin pathway without evidence of matrical differentiation, as well as 4 combined tumors in which a similar Wnt/β-catenin–activated carcinoma component was associated with Merkel cell carcinoma (MCC) or pilomatrical carcinoma. Among the pure tumor cases, 6 of 16 patients were women with a median age of 80 years (range, 58-98 years). Tumors were located on the head and neck (n = 7, 44%), upper limb (n = 4, 25%), trunk (n = 3, 18%), and leg (n = 2, 13%). Metastatic spread was observed in 4 cases resulting in death from disease in 1 patient. Microscopically, all cases were poorly differentiated neoplasms infiltrating the dermis and/or subcutaneous tissue. In 13 cases, solid “squamoid” areas were associated with a basophilic component characterized by rosette/pseudoglandular formation resulting in a biphasic appearance. Three specimens consisted only of poorly differentiated carcinoma lacking rosette formation. Immunohistochemical studies showed frequent expression of EMA (100%), BerEP4 (100%), cytokeratin 7 (94%), chromogranin A (44%), synaptophysin (82%), and cytokeratin 20 (69%). Complete loss of Rb expression was observed in all but 1 case. Nuclear β-catenin and CDX2 expressions were detected in all cases. Recurrent pathogenic somatic mutations were observed in APC (60%), CTNNB1 (40%), and RB1 (n = 47%). Global methylation analysis confirmed that cases with rosette formation constituted a homogeneous tumor group distinct from established skin tumor entities (pilomatrical carcinoma, MCC, and squamous cell carcinoma), although the 3 other cases lacking such morphologic features did not. In addition, we identified 4 combined neoplasms in which there was a component showing a similar poorly differentiated rosette-forming carcinoma demonstrating Rb loss and β-catenin activation associated with either MCC (n = 3) or pilomatrical carcinoma (n = 1). In conclusion, we describe a distinctive neoplasm, for which we propose the term “Wnt/β-catenin–activated rosette-forming carcinoma,” morphologically characterized by the association of rosette formation, squamous and/or neuroendocrine differentiation, diffuse CDX2 expression, Rb loss, and mutations in CTNNB1/APC genes.

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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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