Department of Pathology, Institut of Pathologie Multisite, Hospices Civils de Lyon, University South Lyon Hospital, Pierre-Bénite, France.
Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.
Histopathology. 2024 Aug;85(2):338-346. doi: 10.1111/his.15209. Epub 2024 May 6.
Salivary gland neoplasms (SGN) exhibiting the HMGA2::WIF1 fusion are recognized by their resemblance to histology found in canalicular adenoma. Recently, ~20% of cases among 28 HMGA2::WIF1-rearranged-SGN showed malignancy and adverse outcomes (recurrence, distant metastasis, and disease-specific mortality). Among them, MDM2/CDK4 amplifications were identified in one case. This outcome suggests that the MDM2/CDK4 amplifications could be useful to predict an aggressive course of carcinoma ex-pleomorphic adenoma (CEPA).
We investigated the correlation between HMGA2 fusion and MDM2 amplification in four salivary gland neoplasms, providing detailed clinicopathological features and outcomes. Cases were selected from different institutions. Histological examination, immunohistochemistry, fluorescence in situ hybridization (FISH), RNA sequencing, and whole-exome capture were performed. The cohort included four CEPA cases, all female, aged between 32 and 89 years. Tumours arose from the parotid gland with an average size of 24.5 mm. None exhibited recurrence or distant metastases during the 4-5 months of follow-up. Pathologically, all cases displayed a peculiar atypical nuclei with 'gear-like appearance'. Immunohistochemically, tumours exhibited a biphasic pattern with myoepithelial and ductal differentiation markers. All cases showed HMGA2 overexpression and MDM2 amplification by FISH and RNA sequencing. In a control cohort of MDM2 nonamplified CEPA cases, not exhibiting the peculiar nuclear atypia.
Our findings suggest a strong correlation between HMGA2 alteration/MDM2 amplification and a peculiar nuclear atypia, advocating for their evaluation in biphasic tumours to facilitate accurate diagnosis and tailored posttumour removal monitoring. Further studies are warranted to validate these observations and elucidate their prognostic implications.
具有 HMGA2::WIF1 融合的唾液腺肿瘤（SGN）因其类似于管腔性腺瘤的组织学特征而被识别。最近，在 28 例 HMGA2::WIF1 重排的 SGN 中，约 20%的病例表现出恶性和不良结局（复发、远处转移和疾病特异性死亡率）。其中，一例存在 MDM2/CDK4 扩增。这一结果表明，MDM2/CDK4 扩增可用于预测癌型多形性腺瘤（CEPA）的侵袭性病程。
我们研究了 HMGA2 融合与四种唾液腺肿瘤中 MDM2 扩增之间的相关性，提供了详细的临床病理特征和结果。病例选自不同的机构。进行了组织学检查、免疫组织化学、荧光原位杂交（FISH）、RNA 测序和全外显子捕获。该队列包括四例 CEPA 病例，均为女性，年龄 32 至 89 岁。肿瘤发生于腮腺，平均大小为 24.5mm。在 4-5 个月的随访期间，均无复发或远处转移。病理上，所有病例均显示具有“齿轮状外观”的特殊非典型核。免疫组织化学显示，肿瘤具有肌上皮和导管分化标志物的双相模式。所有病例均显示 FISH 和 RNA 测序的 HMGA2 过表达和 MDM2 扩增。在未表现出特殊核异型性的 MDM2 非扩增 CEPA 病例的对照组中，未观察到 MDM2 扩增。
我们的发现表明 HMGA2 改变/MDM2 扩增与特殊核异型性之间存在很强的相关性，主张在双相肿瘤中评估它们，以促进准确诊断和定制肿瘤切除后监测。需要进一步的研究来验证这些观察结果并阐明它们的预后意义。
