Ovarian squamous cell carcinoma associated with teratoma: a report of six cases with genomic analysis

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.