Knebel Moritz, Agaimy Abbas, Kühn Jan Philipp, Körner Sandrina, Braun Felix, Brust Lukas, Flockerzi Veronika, Wemmert Silke, Balensiefer Benedikt, Schick Bernhard, Yilmaz Umut, Zaito Malek, Bozzato Alessandro, Linxweiler Maximilian
Institute of Otorhinolaryngology, Saarland University, Homburg, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center (UKS), Homburg, Germany.
Front Immunol. 2025 Jul 4;16:1611790. doi: 10.3389/fimmu.2025.1611790. eCollection 2025.
fusion-associated carcinomas of the sinonasal tract are exceedingly rare, with fewer than 100 cases reported worldwide, but probably underrecognized. Recently classified by the WHO as a distinct provisional subtype of non-keratinizing squamous cell carcinoma, these tumors pose significant diagnostic and therapeutic challenges. Their histological resemblance to inverted papillomas and their bland histology in most cases often leads to misdiagnosis, while their aggressive behavior underscores the need for a tailored treatment approach.
We report two cases of fusion-associated carcinomas managed at Saarland University Medical Center. The first case involved a 46-year-old woman who initially presented with recurrent sinonasal inverted papilloma, confirmed through multiple surgical interventions over nearly a decade. In 2023, reevaluation and genetic analysis revealed a fusion. The patient demonstrated an exceptional response to three cycles of neoadjuvant gemcitabine and cisplatin, achieving complete remission on MRI restaging. This allowed a shift to definitive chemoradiotherapy, with sustained disease-free status confirmed by a PET-CT three months post-treatment in July 2024. The second case involved a 66-year-old woman presenting with recurrent inverted papilloma affecting the sinonasal and tympanic regions. Despite multiple surgeries, malignant transformation to invasive squamous cell carcinoma occurred, with lymph node metastasis and intracranial spread. A combined otolaryngological and neurosurgical approach was undertaken, but the disease progressed. The patient passed away in January 2020, with postmortem review of the prior histology and genetic analysis confirming fusion carcinoma that showed bland-looking papilloma-like morphology in the initial specimens and later a high-grade cytology indicating biological progression to poorly differentiated carcinoma.
These cases highlight the aggressive nature of fusion-associated carcinomas and the critical role of genetic profiling in diagnosis and management. The exceptional, first ever reported response to neoadjuvant chemotherapy in one case underscores the potential for personalized treatment strategies, warranting further investigation into targeted therapies for this rare malignancy.
鼻窦融合相关癌极为罕见，全球报道病例不足100例，但可能未得到充分认识。世界卫生组织最近将其归类为非角化性鳞状细胞癌的一种独特的临时亚型，这些肿瘤带来了重大的诊断和治疗挑战。它们在组织学上与内翻性乳头状瘤相似，且在大多数情况下组织学表现平淡，常导致误诊，而其侵袭性则凸显了采用量身定制治疗方法的必要性。
我们报告了在萨尔州大学医学中心治疗的两例融合相关癌病例。第一例为一名46岁女性，最初表现为复发性鼻窦内翻性乳头状瘤，经过近十年的多次手术干预得以确诊。2023年，重新评估和基因分析发现了一种融合。该患者对三个周期的新辅助吉西他滨和顺铂治疗表现出异常反应，在MRI重新分期时实现了完全缓解。这使得治疗方案转向确定性放化疗，2024年7月治疗后三个月的PET-CT证实疾病持续无进展。第二例为一名66岁女性，表现为累及鼻窦和鼓室区域的复发性内翻性乳头状瘤。尽管进行了多次手术，但仍发生了向浸润性鳞状细胞癌的恶性转化，并伴有淋巴结转移和颅内扩散。采取了耳鼻喉科和神经外科联合治疗方法，但疾病仍进展。患者于2020年1月去世，死后对先前的组织学检查和基因分析证实为融合癌，最初标本显示出外观平淡的乳头状瘤样形态，后来出现高级别细胞学表现，提示生物学进展为低分化癌。
这些病例凸显了融合相关癌的侵袭性以及基因谱分析在诊断和管理中的关键作用。其中一例对新辅助化疗的异常反应是首次报道，这凸显了个性化治疗策略的潜力，有必要对这种罕见恶性肿瘤的靶向治疗进行进一步研究。
