Burghout Kimberly S T, Breimer G E, Koppes S, Hazelbag H M, Ooft M L, Raicu G M, Cleton-Jansen A M, van Wezel T, van Eijk R, Terlouw D, van Egmond S L, Smit V T H B M, Rupp N J, Cohen D
Department of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden, ZA 2333, The Netherlands.
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Head Neck Pathol. 2025 May 8;19(1):56. doi: 10.1007/s12105-025-01794-y.
Pleomorphic adenoma is the most common neoplasm of the salivary glands. While the overall risk of malignancy is relatively low, a distinct molecular sub-group harboring HMGA2 alterations seems to show an increased risk of malignant progression to carcinoma ex pleomorphic adenoma.
This study investigates MDM2 amplification in HMGA2-altered pleomorphic adenoma, atypical pleomorphic adenoma, and carcinoma ex pleomorphic adenoma.
In this multicenter, retrospective case series analysis, we examined 37 cases of HMGA2-altered pleomorphic adenoma, carcinoma ex pleomorphic adenoma, and pleomorphic adenoma with atypical features. A total of 18 cases were included from our institutional archives, with 19 additional cases derived from published literature. The cases from our institutes were analyzed for MDM2 amplification using a stepped approach by immunohistochemistry and FISH.
Collectively, an MDM2 amplification was present in 27% of pleomorphic adenoma (4 of 15), compared to 78% of carcinoma ex pleomorphic adenoma (14 of 18) (p-value = 0.003). In the group of pleomorphic adenomas with atypical features, an MDM2 amplification was present in 50% of cases (2 of 4). These findings indicate an association between MDM2 amplification and malignancy. Strikingly, a mixed control group of 12 benign and malignant PLAG1-altered neoplasms showed no immunohistochemical staining for MDM2.
Immunohistochemical MDM2 expression, including MDM2 amplification, is enriched in the group of HMGA2-altered pleomorphic adenoma, and potentially plays role in malignant progression. This study highlights the importance of recognizing the molecular sub-group of HMGA2-altered pleomorphic adenomas and integrate MDM2 analysis into routine diagnostics to corroborate the cytonuclear atypia in these challenging cases.
多形性腺瘤是唾液腺最常见的肿瘤。虽然总体恶变风险相对较低，但携带HMGA2改变的一个独特分子亚组似乎显示出向多形性腺瘤癌变进展的风险增加。
本研究调查MDM2在携带HMGA2改变的多形性腺瘤、非典型多形性腺瘤和多形性腺瘤癌变中的扩增情况。
在这项多中心回顾性病例系列分析中，我们检查了37例携带HMGA2改变的多形性腺瘤、多形性腺瘤癌变和具有非典型特征的多形性腺瘤。其中18例来自我们机构的档案，另外19例来自已发表的文献。对我们机构的病例采用免疫组织化学和荧光原位杂交的分步方法分析MDM2扩增情况。
总体而言，27%的多形性腺瘤（15例中的4例）存在MDM2扩增，相比之下，78%的多形性腺瘤癌变（18例中的14例）存在MDM2扩增（p值 = 0.003）。在具有非典型特征的多形性腺瘤组中，50%的病例（4例中的2例）存在MDM2扩增。这些发现表明MDM2扩增与恶性肿瘤之间存在关联。引人注目的是，一个由12例良性和恶性PLAG1改变的肿瘤组成的混合对照组未显示MDM2的免疫组织化学染色。
包括MDM2扩增在内的免疫组织化学MDM2表达在携带HMGA2改变的多形性腺瘤组中富集，并且可能在恶性进展中起作用。本研究强调了识别携带HMGA2改变的多形性腺瘤分子亚组并将MDM2分析纳入常规诊断以证实这些具有挑战性病例中的细胞核异型性的重要性。
