Sasaki Eiichi, Fujita Yasuko, Masago Katsuhiro, Iwakoshi Akari, Hanai Nobuhiro, Matsushita Hirokazu
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-Ku, Nagoya, Aichi, 464-8681, Japan.
Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Virchows Arch. 2025 May;486(5):1033-1038. doi: 10.1007/s00428-024-04021-1. Epub 2024 Dec 26.
Basal cell adenomas (BCAs) are benign epithelial tumors of the salivary gland, characterized by the proliferation of basaloid and luminal cells. In addition, a distinctive spindle cell stroma, that is immunohistochemically-positive for S100, is often observed in BCAs. Based on the ultrastructural findings, the S100-positive stroma was presumed to originate from neoplastic myoepithelial cells. However, immunohistochemical studies do not provide strong evidence supporting a myoepithelial origin, and the true nature of this stroma remains elusive. The aim of this study was to determine whether the S100-positive stroma was neoplastic through a molecular analysis. We selected 2 cases involving BCAs with at least one S100-positive stromal area within the tumor, measuring ≥ 0.2 × 0.2 mm. CTNNB1 I35T mutations were detected in both tumors by Sanger sequencing. Two areas of S100-positive stroma from these two tumors were successfully dissected by manual microdissection using a stereomicroscope without contamination from the surrounding neoplastic bilayered epithelial cells. Because of the small number of dissected stromal cells, the mutation status of these two areas was analyzed using digital PCR, and CTNNB1 I35T mutations were detected in both. In conclusion, this study demonstrated that the S100-positive stroma of BCAs exhibits a neoplastic nature from a molecular perspective. While future studies are needed to confirm whether the S100-positive stroma originates from myoepithelial cells, BCAs morphologically display tricellular differentiation, with neoplastic spindle-shaped stromal cells along with a bilayered neoplastic epithelium.
基底细胞腺瘤（BCAs）是唾液腺的良性上皮性肿瘤，其特征为基底样细胞和管腔细胞的增殖。此外，在基底细胞腺瘤中常可见一种独特的梭形细胞间质，其S100免疫组化呈阳性。基于超微结构研究结果，推测S100阳性间质起源于肿瘤性肌上皮细胞。然而，免疫组化研究并未提供支持肌上皮起源的有力证据，这种间质的真实性质仍然难以捉摸。本研究的目的是通过分子分析确定S100阳性间质是否为肿瘤性。我们选择了2例肿瘤内至少有一个S100阳性间质区域且大小≥0.2×0.2 mm的基底细胞腺瘤病例。通过桑格测序在这两个肿瘤中均检测到CTNNB1 I35T突变。使用体视显微镜通过手工显微切割成功从这两个肿瘤中分离出两个S100阳性间质区域，且未受到周围肿瘤性双层上皮细胞的污染。由于分离的间质细胞数量较少，使用数字PCR分析这两个区域的突变状态，结果在两个区域均检测到CTNNB1 I35T突变。总之，本研究表明，从分子角度来看，基底细胞腺瘤的S100阳性间质具有肿瘤性。虽然需要进一步研究来证实S100阳性间质是否起源于肌上皮细胞，但基底细胞腺瘤在形态上表现为三细胞分化，具有肿瘤性梭形间质细胞以及双层肿瘤上皮。
