Cubides-Córdoba María Camila, Sánchez-Fernández Paula, Mendoza-Pacas Guillermo E, Cabal Virginia N, García-Marín Rocío, Lorenzo-Guerra Sara Lucila, García-Velasco Fabián, Hermsen Mario A, Llorente José Luis
Department of Otorhinolaryngology and Head and Neck Surgery, Central University Hospital of Asturias, Oviedo, Spain.
Department of Pathological Anatomy, Central University Hospital of Asturias, Oviedo, Spain.
Front Oncol. 2024 Sep 10;14:1448213. doi: 10.3389/fonc.2024.1448213. eCollection 2024.
Human Papillomavirus (HPV) related Multiphenotypic Sinonasal Carcinoma (HMSC) is a rare tumor with features of both atypical squamous cell and adenoid cystic carcinoma, making diagnosis challenging. Approximately 80% of HMSC cases carries HPV type 33 followed by type 35. We present a patient with HMSC. Pathological classification was aided by immunohistochemistry (IHC). The presence of HPV-DNA was tested using PCR and HPV E6/E7 expression by RNA hybridization (RNA ISH). Whole exome sequencing (WES) was used to identify somatic gene mutations and copy number alterations. A 55-year-old male presented with an HMSC in the right nostril. Histological examination showed a solid basaloid subtype with mucinous spaces and ductal structures. IHC showed positive staining for SOX-10, SMA, p40, p63, PanCK, CK8 and MYB. Diffuse positive staining for p16 was observed and PCR and RNA ISH indicated the presence of HPV type 35. The patient was treated with endoscopic surgery and radiotherapy and is currently alive and recurrence-free after 16 months of follow-up. WES revealed 38 somatic sequence variants and several chromosomal regions with copy number alterations, including a copy number gain at 6q23 where is located. and are some of the genes whose mutations were indicated as probably pathogenic. We did not find mutations predictive for drug response according to the ESMO Scale for Clinical Actionability of Molecular Targets database. This is the first report of WES analysis of an HMSC, in this case associated with HPV type 35. The detected mutation in and the overexpression of may serve as molecular targets for personalized therapy.
人乳头瘤病毒（HPV）相关的多表型鼻窦癌（HMSC）是一种罕见肿瘤，具有非典型鳞状细胞癌和腺样囊性癌的特征，这使得诊断具有挑战性。大约80%的HMSC病例携带33型HPV，其次是35型。我们报告了一例HMSC患者。免疫组织化学（IHC）辅助进行病理分类。使用聚合酶链反应（PCR）检测HPV-DNA的存在，并通过RNA杂交（RNA ISH）检测HPV E6/E7表达。全外显子测序（WES）用于识别体细胞基因突变和拷贝数改变。一名55岁男性患者右侧鼻孔出现HMSC。组织学检查显示为具有黏液间隙和导管结构的实性基底样亚型。IHC显示SOX-10、平滑肌肌动蛋白（SMA）、p40、p63、广谱细胞角蛋白（PanCK）、细胞角蛋白8（CK8）和MYB呈阳性染色。观察到p16弥漫性阳性染色，PCR和RNA ISH表明存在35型HPV。该患者接受了内镜手术和放疗，目前存活，随访16个月后无复发。WES揭示了38个体细胞序列变异以及几个具有拷贝数改变的染色体区域，包括位于6q23的拷贝数增加。 和 是一些其突变被表明可能具有致病性的基因。根据分子靶点临床可操作性的欧洲肿瘤内科学会（ESMO）量表数据库，我们未发现预测药物反应的突变。这是首例对HMSC进行WES分析的报告，在本病例中与35型HPV相关。检测到的 和 的过表达可能作为个性化治疗的分子靶点。
