Peculiar nuclear atypia associated with MDM2 gene amplification in carcinoma ex-pleomorphic adenoma harbouring an alteration of HMGA2

IF 3.9 2区医学 Q2 CELL BIOLOGY

Histopathology Pub Date : 2024-05-06 DOI:10.1111/his.15209

Ziyad Alsugair, Maxime Fieux, Françoise Descotes, Jonathan Lopez, Carolle Cordonnier, Juliette Russel, Anne Champagnac, Daniel Pissaloux, Philippe Céruse, Pierre Philouze, Nazim Benzerdjeb

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引用次数: 0

Abstract

Aims

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).

Methods and Results

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.

Conclusions

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.

Abstract Image

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携带 HMGA2 基因改变的癌前乳头状腺瘤中与 MDM2 基因扩增相关的特殊核不典型性。

目的：唾液腺肿瘤（SGN）表现出HMGA2::WIF1融合，与管状腺瘤的组织结构相似。最近，在 28 例 HMGA2::WIF1-重组 SGN 中，约 20% 的病例出现恶变和不良后果（复发、远处转移和疾病特异性死亡率）。其中，有一例发现了 MDM2/CDK4 扩增。这一结果表明，MDM2/CDK4扩增可用于预测癌前多形性腺瘤（CEPA）的侵袭性病程：我们研究了四种唾液腺肿瘤中HMGA2融合与MDM2扩增之间的相关性，并提供了详细的临床病理特征和结果。病例选自不同机构。对病例进行了组织学检查、免疫组化、荧光原位杂交（FISH）、RNA测序和全外显子组捕获。队列中包括四例CEPA病例，均为女性，年龄在32至89岁之间。肿瘤来自腮腺，平均大小为24.5毫米。在4-5个月的随访期间，无一例出现复发或远处转移。病理上，所有病例均显示出特殊的非典型细胞核，呈 "齿轮样外观"。免疫组化结果显示，肿瘤呈双相型，有肌上皮和导管分化标记物。通过 FISH 和 RNA 测序，所有病例均显示 HMGA2 过表达和 MDM2 扩增。在对照组中，MDM2未扩增的CEPA病例未表现出特殊的核不典型性：我们的研究结果表明，HMGA2改变/MDM2扩增与奇特的核不典型性之间存在很强的相关性，主张在双相肿瘤中对其进行评估，以促进准确诊断和有针对性的肿瘤切除后监测。为验证这些观察结果并阐明其对预后的影响，有必要开展进一步的研究。

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来源期刊

Histopathology 医学-病理学

CiteScore

10.20

自引率

4.70%

发文量

239

审稿时长

1 months

期刊介绍： Histopathology is an international journal intended to be of practical value to surgical and diagnostic histopathologists, and to investigators of human disease who employ histopathological methods. Our primary purpose is to publish advances in pathology, in particular those applicable to clinical practice and contributing to the better understanding of human disease.

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