Department of Oral and Maxillofacial Pathology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Oral & Maxillofacial Oncology and Surgery, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Head Neck Pathol. 2023 Dec;17(4):1026-1033. doi: 10.1007/s12105-023-01580-8. Epub 2023 Sep 21.
Squamous cell carcinoma (SCC) is the most common oral malignancy, and somatic mutations in some driver genes have been implicated in SCC development. Clear cell SCC (CCSCC) is a rare histological variant of SCC, and various clear cell neoplasms must be considered in the differential diagnosis of CCSCC in the oral cavity. Based on a limited number of CCSCC cases reported in the oral cavity, CCSCC is considered an aggressive variant of SCC with a poor prognosis; however, its genetic characteristics remain unknown.
A maxillary gingival tumor in an 89-year-old female was described and investigated using immunohistochemical staining, special staining, fluorescence in situ hybridization, and next-generation sequencing (NGS) with a custom panel of driver genes, including those associated with SCC and clear cell neoplasm development.
Histopathological examination revealed a proliferation of atypical epithelial cells with abundant clear cytoplasm and enlarged and centrally placed round nuclei. The tumor was exophytic with deep, penetrating proliferation. The atypical clear cells were continuous with the conventional SCC cells. Immunohistochemical analysis showed that the clear cells were positive for CK AE1/AE3 and CK5/6 and nuclear-positive for p63. In contrast, the clear cells were negative for αSMA, S100, HMB45, Melan-A, CD10, and p16. p53 immunoreactivity exhibited a wild-type expression pattern. Additionally, the clear cells were positive for periodic acid-Schiff (PAS) and negative for diastase-PAS, mucicarmine, and Alcian blue. Based on these results, the diagnosis of CCSCC was confirmed. Molecular analysis of the clear cells identified PIK3CA p.E542K (c.1624G>A) and HRAS p.G12A (c.35 G>C) somatic mutations classified as oncogenic. No pathogenic variants were identified in TP53, EWSR1, AKT1, PTEN, BRAF, KRAS, NRAS, RASA1, or MAML2.
We report a case of CCSCC of the oral cavity with PIK3CA and HRAS mutations. The identification of PIK3CA and/or HRAS mutations is rare in SCC; however, both mutations are important potential targets for antitumor therapy. A detailed analysis of gene mutations in CCSCC may lead to a better understanding of its biological behavior and an improved prognosis, as well as a differential diagnosis from other clear cell neoplasms.
鳞状细胞癌（SCC）是最常见的口腔恶性肿瘤，一些驱动基因的体细胞突变与 SCC 的发展有关。透明细胞 SCC（CCSCC）是 SCC 的一种罕见组织学变异体，在口腔中诊断 CCSCC 时必须考虑各种透明细胞肿瘤。基于口腔中报道的少数 CCSCC 病例，CCSCC 被认为是一种预后不良的 SCC 侵袭性变体；然而，其遗传特征仍不清楚。
描述并通过免疫组织化学染色、特殊染色、荧光原位杂交和下一代测序（NGS）对一位 89 岁女性上颌牙龈肿瘤进行研究，该 NGS 使用了一个包括 SCC 和透明细胞肿瘤发展相关基因的定制驱动基因面板。
组织病理学检查显示，上皮细胞增生，细胞质丰富，细胞核呈圆形且居中。肿瘤呈外生性，有深层穿透性增生。异型透明细胞与常规 SCC 细胞连续。免疫组织化学分析显示，透明细胞 CKAE1/AE3 和 CK5/6 阳性，核 p63 阳性。相反，透明细胞 αSMA、S100、HMB45、Melan-A、CD10 和 p16 阴性。p53 免疫反应呈野生型表达模式。此外，透明细胞 PAS 阳性，PAS 酶阳性，黏蛋白阴性，Alcian blue 阴性。基于这些结果，确诊为 CCSCC。对透明细胞的分子分析发现 PIK3CA p.E542K（c.1624G>A）和 HRAS p.G12A（c.35 G>C）体细胞突变被归类为致癌突变。未在 TP53、EWSR1、AKT1、PTEN、BRAF、KRAS、NRAS、RASA1 或 MAML2 中发现致病性变异。
我们报告了一例口腔 CCSCC，存在 PIK3CA 和 HRAS 突变。在 SCC 中，PIK3CA 和/或 HRAS 突变很少见；然而，这两种突变都是抗肿瘤治疗的重要潜在靶点。对 CCSCC 基因突变的详细分析可能有助于更好地了解其生物学行为和预后，并与其他透明细胞肿瘤进行鉴别诊断。
