卵巢鳞状细胞癌（SCC），尤其是起源于畸胎瘤的肉瘤样变异，是一种罕见的恶性肿瘤，具有不良的临床结局。其分子遗传变异尚未完全记录。本研究旨在描述这种罕见实体的分子特征，并提供潜在的治疗靶点。我们分析了六例原发性卵巢SCC的临床病理和免疫组织化学特征。这些病例接受有针对性的下一代测序以检测基因组特征。我们发现所有六例卵巢SCC（四例常规型和两例肉瘤样SCC）均与成熟囊性畸胎瘤相关。第三例（FIGO IIIa期）和第四例（IIb期）患者分别在10个月和11个月死于疾病。其余患者（三例I期和一例IIc期），包括两例肉瘤样SCC，存活期间未见疾病证据，存活时间为28-72个月。所有患者均显示PD-L1表达（肿瘤比例评分：范围10-78%，中位数41%；综合阳性评分：范围12-85，中位数42），并具有较高的肿瘤突变负荷（范围13.4-25.7个突变/Mb，中位数16.5）。最常见的重复突变包括PIK3CA（4/6），TP53（4/6），TERT启动子（4/6），CDKN2A（3/6）。在5/6患者中发现了同源重组修复途径基因（BLM，ATM，BRCA1，BRIP1和ATM）的突变。肉瘤样SCC与常规SCC具有类似的突变谱，未发现肉瘤样SCC特有的经常性遗传突变。我们的研究表明，由于PD-L1表达和基因组特征，免疫检查点抑制剂和/或PARP抑制剂对原发性卵巢SCC患者可能具有潜在的益处。卵巢肉瘤样SCC可能与常规SCC存在克隆关系。将来的多机构、临床和分子研究将巩固这些发现。 © 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Ovarian squamous cell carcinoma (SCC), particularly the sarcomatoid variant, arising from teratoma is a rare malignant tumour with unfavourable clinical outcomes. Its molecular genetic alterations have not been well-documented to date. This study aims to characterise the molecular features and to provide potential therapeutic targets in this rare entity. We analysed the clinicopathological and immunohistochemical features of six primary ovarian SCC. These cases were subject to targeted next-generation sequencing to detect genomic features. We found that all six ovarian SCC (four conventional and two sarcomatoid SCC) were associated with mature cystic teratomas. Patient 3 (FIGO stage IIIa) and Patient 4 (stage IIb) died of disease at 10 and 11 months, respectively. The remaining patients (three with stage I and one with IIc) including the two with sarcomatoid SCC, were alive with no evidence of disease at 28-72 months. All patients showed PD-L1 expression (tumour proportion score: range 10-78%, median 41%; combined positive score: range 12-85, median 42) and a high tumour mutation burden (range 13.4-25.7 mutations/Mb, median 16.5). The most frequently recurrent mutations included PIK3CA (4/6), TP53 (4/6), TERT promoter (4/6), CDKN2A (3/6). Mutations in homologous recombination repair pathway genes (BLM, ATM, BRCA1, BRIP1 and ATM) were found in 5/6 patients. The sarcomatoid SCC shared a similar mutational profile with conventional SCC, and no recurrent genetic mutations exclusively in sarcomatoid SCC were identified. Our study suggests the potential benefits of immune checkpoint inhibitors and/or PARP inhibitors in patients with primary ovarian SCC on account of PD-L1 expression and genomic features. Ovarian sarcomatoid SCC may be clonally related to the conventional SCC. A multiple-institutional, clinical and molecular study will consolidate these findings in the future.Copyright © 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.