Barbieux Simon, Jouenne Fanélie, Machet Marie-Christine, Fraitag Sylvie, Macagno Nicolas, Battistella Maxime, Cribier Bernard, Sohier Pierre, Laurent-Roussel Sara, Carlotti Agnès, Beltzung Fanny, Jullié Marie-Laure, Moulonguet Isabelle, Basset-Seguin Nicole, Deschamps Lydia, Mourah Samia, Samimi Mahtab, Guyétant Serge, Kervarrec Thibault
Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France; Platform of Somatic Tumor Molecular Genetics, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France.
Department of Tumors Genomics and Pharmacology, Hôpital Saint-Louis, AP-HP, Paris, France.
Pathology. 2025 Feb;57(1):49-56. doi: 10.1016/j.pathol.2024.06.013. Epub 2024 Sep 17.
Naevoid basal cell carcinoma syndrome (NBCCS) is a rare genodermatosis caused by germline mutations in genes of the Sonic Hedgehog (SHH) pathway and is characterised by early onset of multiple basal cell carcinomas (BCCs). Although skin tumours with follicular differentiation, notably basaloid follicular hamartoma (BFH), have been reported in NBCCS, their relations with BCC are poorly defined. In this context, the aim of this study was to clarify morphological, immunohistochemical and molecular features of BFH arising in a context of NBCCS. A total of 140 skin tumours from NBCCS and 140 control BCC tumours were reviewed, blinded to clinical data and classified as BCC or BFH. The morphological characteristics of these two groups were then compared. Twenty cases were submitted for immunohistochemical and molecular analysis. Thirty-three tumours among the exploratory cohort were classified as BFH and were exclusively detected in NBCCS patients. Histopathological criteria that were significantly different from BCC were as follows: a small size (<1.5 mm), connection to a hair follicle, arborescent organoid architecture, lack of cytological atypia and infundibulocystic differentiation. Immunohistochemical analysis confirmed activation of the SHH pathway in these lesions. Targeted next-generation sequencing suggested that MYCN and GLI2/3 amplifications and TP53 mutations might be involved in progression of these follicular tumours to BCC. Our study confirms the high prevalence of BFH, representing up to 24% of skin tumours in NBCCS and potentially being BCC precursors.
痣样基底细胞癌综合征（NBCCS）是一种罕见的遗传性皮肤病，由 Sonic Hedgehog（SHH）信号通路基因的种系突变引起，其特征是多发基底细胞癌（BCC）发病早。尽管在 NBCCS 中已报道有具有毛囊分化的皮肤肿瘤，尤其是基底样毛囊错构瘤（BFH），但其与 BCC 的关系尚不明确。在此背景下，本研究的目的是阐明 NBCCS 背景下发生的 BFH 的形态学、免疫组化和分子特征。对来自 NBCCS 的 140 例皮肤肿瘤和 140 例对照 BCC 肿瘤进行了回顾性分析，在不了解临床数据的情况下将其分类为 BCC 或 BFH。然后比较这两组的形态学特征。选取 20 例进行免疫组化和分子分析。探索性队列中的 33 个肿瘤被分类为 BFH，且仅在 NBCCS 患者中检测到。与 BCC 有显著差异的组织病理学标准如下：体积小（<1.5 mm）、与毛囊相连、树枝状类器官结构、缺乏细胞异型性和漏斗状囊肿分化。免疫组化分析证实这些病变中 SHH 信号通路激活。靶向二代测序表明，MYCN 和 GLI2/3 扩增以及 TP53 突变可能参与这些毛囊肿瘤向 BCC 的进展。我们的研究证实了 BFH 的高患病率，在 NBCCS 中占皮肤肿瘤的 24%，可能是 BCC 的前体。
